Updated on 2022/12/02

写真a

 
NAKASHIMA, Takuji
 
Scopus Paper Info  
Paper Count: 0  Citation Count: 0  h-index: 13

Citation count denotes the number of citations in papers published for a particular year.

Affiliation
Affiliated organization, Research Innovation Center
Job title
Senior Researcher(Professor)

Concurrent Post

  • Faculty of Science and Engineering   School of Advanced Science and Engineering

Education

  •  
    -
    1991

    Nagasaki University  

Degree

  • Nagasaki University   pharmacy

Research Experience

  • 2020
    -
    Now

    早稲田大学

  • 2008
    -
    2020

    北里大学

  • 2006
    -
    2008

    製品評価技術基盤機構

  • 2002
    -
    2006

    Nagasaki Industrial Promotion Foundation

  • 1991
    -
    2002

    ポーラ化成工業(株)新薬研究所

Professional Memberships

  • 2021.03
    -
    Now

    マリンバイオテクノロジー学会

  •  
     
     

    日本放線菌学会

  •  
     
     

    日本生物工学会

  •  
     
     

    日本農芸化学会

 

Research Areas

  • Applied microbiology   Microbiology, Chemical biology, Natural compounds, Analytical chemistry

Research Interests

  • 応用微生物学

  • 創薬

  • 分析化学

  • 天然物化学

Papers

  • New nitrogen-compounds, penicidones E and F, produced by the fungal strain Oidiodendron sp. FKI-7498.

    Rei Miyano, Hirotaka Matsuo, Takayuki Mokudai, Mayuka Higo, Kenichi Nonaka, Yoshimi Niwano, Kazuro Shiomi, Yōko Takahashi, Satoshi Ōmura, Takuji Nakashima

    Bioscience, biotechnology, and biochemistry    2022.11  [Refereed]  [International journal]

    Authorship:Corresponding author

     View Summary

    The nitrogen rule in mass spectrometry was used to search for new nitrogen-compounds from microbial metabolites. During this program, two new nitrogen-containing compounds, penicidones E and F, were discovered from the filamentous fungal strain FKI-7498, which was isolated from soil collected in Tokushima, Japan and identified as Oidiodendron sp. by sequence analysis of the internal transcribed spacer region, including 5.8S ribosomal RNA. The structures of penicidones E and F were determined by mass spectrometry, nuclear magnetic resonance spectroscopy, and chemical modification analyses. These analyses revealed that penicidones E and F have a core structure of 3,5-dihydroxy-2-(4-pyridone-3-carbonyl)benzoic acid. Penicidone E exhibited hydroxyl radical scavenging activity.

    DOI PubMed

  • Detection and characterization of new mangromicin analogs by tandem mass spectrometry.

    Yoshiyuki Kamiya, Takuji Nakashima, Takako Taniguchi, Yōko Takahashi, Satoshi Ōmura, Hisaaki Taniguchi

    Bioscience, biotechnology, and biochemistry    2022.09  [Refereed]  [International journal]

    Authorship:Corresponding author

     View Summary

    Many useful natural products are usually screened based on their biological activities. On the other hand, various natural products can be detected based on their physicochemical properties. We have already reported the isolation and characterization of mangromicins from a cultural broth of Lechevalieria aerocolonigenes K10-0216 using physicochemical screening. In this report, we have conducted the mass spectrometry-based screening of new mangromicin analogs based on the neutral loss pattern originated from the unique cyclopentadecane skeleton of mangromicins. Two novel analogs were detected showing characteristic neutral loss pattern found in eight known mangromicin analogs. We propose the structures of the newly-found analogs based on the mass spectrometric as well as genomic and metabolic pathway data.

    DOI PubMed

  • Sattahipmycin, a Hexacyclic Xanthone Produced by a Marine-Derived Streptomyces.

    Kantinan Leetanasaksakul, Wilaiwan Koomsiri, Takuya Suga, Hirotaka Matsuo, Rei Hokari, Pakorn Wattana-Amorn, Yo Ko Takahashi, Kazuro Shiomi, Takuji Nakashima, Yuki Inahashi, Arinthip Thamchaipenet

    Journal of natural products   85 ( 5 ) 1211 - 1217  2022.05  [Refereed]  [International journal]

     View Summary

    Sattahipmycin was isolated from the mycelium of marine-derived Streptomyces sp. GKU 257-1 by following the antibiofilm activity against E. coli NBRC 3972 throughout the purification steps. The structure of sattahipmycin was determined to be a new polycyclic xanthone related to xantholipin but lacking a dioxymethylene and a chlorinated carbon. This compound showed activity toward Gram-positive bacteria and Plasmodium falciparum, antibiofilm formation of Escherichia coli, and cytotoxicity to human cancer cell lines. Using genome sequence data, a biosynthetic pathway leading to sattahipmycin has been proposed involving an uncharacterized type II polyketide synthase biosynthetic gene cluster.

    DOI PubMed

    Scopus

  • Raman Microspectroscopy Imaging Analysis of Extracellular Vesicles Biogenesis by Filamentous Fungus Penicilium chrysogenum.

    Ashok Zachariah Samuel, Shumpei Horii, Takuji Nakashima, Naoko Shibata, Masahiro Ando, Haruko Takeyama

    Advanced biology     e2101322  2022.03  [Refereed]  [International journal]

     View Summary

    The mechanism of production of extracellular vesicles (EVs) and their molecular contents are of great interest due to their diverse roles in biological systems and are far from being completely understood. Even though cellular cargo releases mediated by EVs have been demonstrated in several cases, their role in secondary metabolite production and release remains elusive. In this study, this aspect is investigated in detail using Raman microspectroscopic imaging. Considerable evidence is provided to suggest that the release of antibiotic penicillin by the filamentous fungus Penicillium chrysogenum involves EVs. Further, the study also reveals morphological modifications of the fungal body during biogenesis, changes in cell composition at the locus of biogenesis, and major molecular contents of the released EVs. The results suggest a possible general role of EVs in the release of antibiotics from the producing organisms.

    DOI PubMed

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    3
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  • Trehangelins ameliorate inflammation-induced skin senescence by suppressing the epidermal YAP-CCN1 axis.

    Mami Yokota, Yoshiyuki Kamiya, Tamie Suzuki, Shinsuke Ishikawa, Akira Takeda, Shinya Kondo, Takeshi Tohgasaki, Takuji Nakashima, Yoko Takahashi, Satoshi Ōmura, Tetsuhito Sakurai

    Scientific reports   12 ( 1 ) 952 - 952  2022.01  [Refereed]  [International journal]

     View Summary

    Trehangelins (THG) are newly identified trehalose compounds derived from broth cultures of an endophytic actinomycete, Polymorphospora rubra. THG are known to suppress Cellular Communication Network factor 1 (CCN1), which regulates collagen homeostasis in the dermis. Although the physical properties of THG suggest a high penetration of the stratum corneum, the effect of THG on the epidermis has not been reported. Here we describe a possible mechanism involved in skin aging focusing on the effect of THG on epidermal CCN1. This study shows that: (1) THG suppress epidermal CCN1 expression by inhibiting the translocation of Yes-Associated Protein (YAP) to nuclei. (2) Epidermal CCN1, localized at the basement membrane, regulates the balance between the growth and differentiation of keratinocytes. (3) Keratinocytes secrete more CCN1 than fibroblasts, which leads to disruption of the basement membrane and extracellular matrix components. (4) The secretion of CCN1 from keratinocytes is increased by ultraviolet B exposure, especially in aged keratinocytes, and deteriorates the elastic fiber structures in the underlying dermis. (5) Topical application of THG ameliorates the structure of the basement membrane in ex vivo human skin explants. Taken together, THG might be a promising treatment for aged skin by suppressing the aberrant YAP-CCN1 axis.

    DOI PubMed

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  • Actinomadura violacea sp. nov., a madurastatin A1-producing strain isolated from lichen in Thailand.

    Pawina Kanchanasin, Wongsakorn Phongsopitanun, Masahiro Yuki, Takuji Kudo, Moriya Ohkuma, Takuji Nakashima, Somboon Tanasupawat

    International journal of systematic and evolutionary microbiology   71 ( 12 )  2021.12  [Refereed]  [International journal]

     View Summary

    An actinomycete strain, LCR2-06T, isolated from a lichen sample on rock collected from Chiang Rai Province (Pong Phra Bat Waterfall), Thailand, was characterized using a polyphasic approach. The strain grew at 25-45 °C, pH 6-11 and on International Streptomyces Project 2 agar plate with 5 % (w/v) NaCl. It contained meso-diaminopimelic acid as the diamino acid in whole-cell hydrolysates. Rhamnose, ribose, xylose, madurose, glucose and galactose were detected as whole-cell sugar hydrolysates. Mycolic acids were absent. The N-acyl type of muramic acid was acetyl. The strain contained C16 : 0, TBSA 10-methyl C18 : 0 and 2-hydroxy C16 : 0 as the predominant fatty acids and MK-9(H6), MK-9(H4) and MK-9(H8) as the major menaquinones. The major polar lipids were diphosphatidylglycerol, phosphatidylinositol and unidentified phospholipid. The draft genome of strain LCR2-06T was closely related to Actinomadura barringtoniae TBRC 7225T (99.2 %), Actinomadura nitritigenes NBRC 15918T (98.8 %), Actinomadura montaniterrae TISTR 2400T (98.5 %) and Actinomadura physcomitrii JCM 33455T (97.9 %). The draft genome of LCR2-06T was 11.1 Mb with 10 588 coding sequences with an average G+C content of 72.7 mol%. Results of genomic analysis revealed that the ANIb and ANIm values between strain LCR2-06T and A. montaniterrae TISTR 2400T were 90.0 and 92.0 %, respectively. The digital DNA-DNA hybridization value was 43.9 % in comparison with the draft genome of A. montaniterrae TISTR 2400T. The strain produced an antibacterial compound active against Bacillus subtilis ATCC 6633 and Kocuria rhizophila ATCC 9341. The results of taxonomic analysis suggested that strain LCR2-06T represented a novel species of the genus Actinomadura for which the name Actinomadura violacea sp. nov. is proposed. The type strain is LCR2-06T (=JCM 33065T=KCTC 49547T=NBRC 114810T=LMG 32136T=TISTR 2935T).

    DOI PubMed

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  • Identification and Analysis of the Biosynthetic Gene Cluster for the Indolizidine Alkaloid Iminimycin in Streptomyces griseus

    Hayama Tsutsumi, Yohei Katsuyama, Takeaki Tezuka, Rei Miyano, Yuki Inahashi, Yoko Takahashi, Takuji Nakashima, Yasuo Ohnishi

    Chembiochem   23   e202100517  2021.11  [Refereed]

    DOI

    Scopus

  • Nanaomycin K inhibited epithelial mesenchymal transition and tumor growth in bladder cancer cells in vitro and in vivo.

    Koichi Kitagawa, Katsumi Shigemura, Aya Ishii, Takuji Nakashima, Hirotaka Matsuo, Yoko Takahashi, Satoshi Omura, Jun Nakanishi, Masato Fujisawa

    Scientific reports   11 ( 1 ) 9217 - 9217  2021.04  [Refereed]  [International journal]

     View Summary

    Nanaomycin K, derived from Streptomyces rosa subsp. notoensis OS-3966T, has been discovered to have inhibitory bioactivity on epithelial-mesenchymal transition (EMT), an important mechanism of cancer cell invasion and migration. In this study, we examined the anti-EMT and anti-tumor effect of nanaomycin K in bladder cancer, where EMT has important roles in progression. We treated two bladder cancer lines, non-muscle-invasive KK47 and muscle-invasive T24, with nanaomycin K to determine the effects on cell proliferation, apoptosis and expression of EMT markers in vitro. Wound-healing assays were performed to assess cell invasion and migration. We conducted an in vivo xenograft study in which mice were inoculated with bladder cancer cells and treated with intratumoral administration of nanaomycin K to investigate its anti-tumor and EMT inhibition effects. As the results, nanaomycin K (50 µg/mL) significantly inhibited cell proliferation in KK47 (p < 0.01) and T24 (p < 0.01) in the presence of TGF-β, which is an EMT-inducer. Nanaomycin K (50 µg/mL) also significantly inhibited cell migration in KK47 (p < 0.01) and T24 (p < 0.01), and induced apoptosis in both cell lines in the presence of TGF-β (p < 0.01). Nanaomycin K increased the expression of E-cadherin and inhibited the expression of N-cadherin and vimentin in both cell lines. Nanaomycin K also decreased expression of Snail, Slug, phospho-p38 and phospho-SAPK/JNK especially in T24. Intratumoral administration of nanaomycin K significantly inhibited tumor growth in both KK47 and T24 cells at high dose (1.0 mg/body) (p = 0.009 and p = 0.003, respectively) with no obvious adverse events. In addition, nanaomycin K reversed EMT and significantly inhibited the expression of Ki-67 especially in T24. In conclusion, we demonstrated that nanaomycin K had significant anti-EMT and anti-tumor effects in bladder cancer cells, suggesting that nanaomycin K may be a therapeutic candidate for bladder cancer treatment.

    DOI PubMed

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  • Aldsulfin, a novel unusual anti-mannheimiosis epithiodiketopiperazine antibiotic produced by Lasiodiplodia pseudotheobromae FKI-4499.

    Kazunari Sakai, Masato Iwatsuki, Masato Iizuka, Yukihiro Asami, Kenichi Nonaka, Rokuro Masuma, Mami Takizawa, Takuji Nakashima, Toshiyuki Tokiwa, Kazuro Shiomi, Satoshi Ōmura

    The Journal of antibiotics   74 ( 6 ) 363 - 369  2021.03  [Refereed]  [Domestic journal]

     View Summary

    An anti-mannheimiosis agent, aldsulfin, was isolated from a culture broth of the fungus Lasiodiplodia pseudotheobromae FKI-4499, together with a known compound, lasiodipline C, using bioassay-guided fractionation. Spectroscopic analysis of aldsulfin, using NMR, mass spectrometry, and CD analyses revealed it to be an epithiodiketopiperazine with an unstable and unusual hemithioaminal moiety. Aldsulfin showed antibacterial activity against Mannheimia haemolytica and Pasteurella multocida.

    DOI PubMed

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    3
    Citation
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  • On Selecting a Suitable Spectral Matching Method for Automated Analytical Applications of Raman Spectroscopy.

    Ashok Zachariah Samuel, Ryo Mukojima, Shumpei Horii, Masahiro Ando, Soshi Egashira, Takuji Nakashima, Masato Iwatsuki, Haruko Takeyama

    ACS omega   6 ( 3 ) 2060 - 2065  2021.01  [Refereed]  [International journal]

     View Summary

    Raman spectra are molecular structure-specific and hence are employed in applications requiring chemical identification. The advent of efficient handheld and smartphone-based Raman instruments is promoting widespread applications of the technique, which often involve less trained end users. Software modules that enable spectral library searches based on spectral pattern matching is an essential part of such applications. The Raman spectrum recorded by end users will naturally have varying levels of signal to noise (SN), baseline fluctuations, etc., depending on the sample environment. Further, in biological, forensic, food, pharmaceuticals, etc., fields where a vast amount of Raman spectral data is generated, careful removal of background is often impossible. In other words, a 100% match between the library spectrum and user input cannot be often guaranteed or expected. Often, such influences are discounted upon developing mathematical methods for general applications. In this manuscript, we carefully examine how such effects would determine the results of spectral similarity-based library search. We show that several popular mathematical spectral matching approaches give incorrect results under the influence of small changes in the baseline and/or the noise. We also discuss the points to be carefully considered while generating a spectral library. We believe our results will be a guiding note for developing applications of Raman spectroscopy that uses a standard spectral library and mathematical spectral matching.

    DOI PubMed

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    7
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  • Detection of Penicillin G Produced by Penicillium chrysogenum with Raman Microspectroscopy and Multivariate Curve Resolution-Alternating Least-Squares Methods.

    Shumpei Horii, Masahiro Ando, Ashok Zachariah Samuel, Akira Take, Takuji Nakashima, Atsuko Matsumoto, Yo Ko Takahashi, Haruko Takeyama

    Journal of natural products   83 ( 11 ) 3223 - 3229  2020.11  [Refereed]  [International journal]

     View Summary

    Raman microspectroscopy is a minimally invasive technique that can identify molecules without labeling. In this study, we demonstrate the detection of penicillin G inside Penicillium chrysogenum KF425 fungal cells. Raman spectra acquired from the fungal cells had highly overlapped spectroscopic signatures and hence were analyzed with multivariate curve resolution by alternating least-squares (MCR-ALS) to extract the spectra of individual molecular constituents. In addition to detecting spatial distribution of multiple constituents such as proteins and lipids inside the fungal body, we could also observe the subcellular localization of penicillin G. This methodology has the potential to be employed in screening the production of bioactive compounds by microorganisms.

    DOI PubMed

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    11
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  • Hatsusamides A and B: Two New Metabolites Produced by the Deep-Sea-Derived Fungal Strain Penicillium steckii FKJ-0213

    Rei Hokari, Aki Ishiyama, Masato Iwatsuki, Mayuka Higo, Kenichi Nonaka, Yuriko Nagano, Yoko Takahashi, Satoshi Ōmura, Takuji Nakashima

    Marine Drugs   18 ( 10 )  2020.10  [Refereed]  [International journal]

    Authorship:Corresponding author

     View Summary

    Two new nitrogen-containing metabolites, designated hatsusamide A (1) and B (2), were isolated from a culture broth of Penicilliumsteckii FKJ-0213 together with the known compounds tanzawaic acid B (3) and trichodermamide C (4) by physicochemical (PC) screening. The structures of 1 and 2 were determined as a tanzawaic acid B-trichodermamide C hybrid structure and a new analog of aspergillazines, respectively. The absolute configuration of 1 was determined by comparing the values of tanzawaic acid B and trichodermamide C in the literatures, such as 1H-nuclear magnetic resonance (1H-NMR) data and optical rotation, after hydrolysis of 1. Compounds 1-4 were evaluated for cytotoxicity and anti-malarial activities. Compounds 1 and 3 exhibited weak anti-malarial activity at half-maximal inhibitory concentration (IC50) values of 27.2 and 78.5 µM against the K1 strain, and 27.9 and 79.2 µM against the FCR3 strain of Plasmodium falciparum, respectively. Furthermore, 1 exhibited cytotoxicity against HeLa S3, A549, Panc1, HT29 and H1299 cells, with IC50 values of 15.0, 13.7, 12.9, 6.8, and 18.7 μM, respectively.

    DOI PubMed

  • Absolute structure and anti-oxidative activity of chaetochiversin C isolated from fungal strain Neocosmospora sp. FKI-7792 by physicochemical screening.

    Hirotaka Matsuo, Tomoyasu Hirose, Takayuki Mokudai, Kenichi Nonaka, Yoshimi Niwano, Toshiaki Sunazuka, Yōko Takahashi, Satoshi Ōmura, Takuji Nakashima

    The Journal of general and applied microbiology   66 ( 3 ) 181 - 187  2020.08  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    A new chaetochiversin analog, designated chaetochiversin C (1), was discovered from a cultured broth of fungal strain FKI-7792 by physicochemical screening. This strain was identified as a member of genus Neocosmospora based on morphology and DNA barcoding. The partially relative configuration of 1 was determined by 13C-NMR chemical shifts of the acetonide analog of 1. The absolute configuration was determined using an advanced Mosher's method. Compound 1 was assessed for anti-tumor, anti-microbial, and anti-malarial activities, and its ability to scavenge or quench reactive oxygen species (ROS), such as superoxide anion radicals, hydroxy radicals and singlet oxygen (1O2). Compound 1 showed a quenching effect on 1O2.

    DOI PubMed

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    1
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  • Oral administration of trehangelin-A alleviates metabolic disorders caused by a high-fat diet through improvement of lipid metabolism and restored beneficial microbiota

    Hiroki Ishikawa, Satoshi Ino, Takuji Nakashima, Hirotaka Matsuo, Yoko Takahashi, Chikara Kohda, Satoshi Omura, Masayuki Iyoda, Kazuo Tanaka

    OBESITY RESEARCH & CLINICAL PRACTICE   14 ( 4 ) 360 - 367  2020.07  [Refereed]  [International journal]

     View Summary

    The present study investigated whether or not the oral administration of trehangelin-A (THG-A) is effective for metabolic disorders caused by a high-fat diet, as we previously showed that the intraperitoneal administration of THG-A improved metabolic disorders caused by a high-fat diet. Mice received a con-trol diet or high-fat diet for eight weeks. Concurrently, mice were orally administered 0.2 ml/mouse phosphate-buffered saline (PBS) or 1 or 10 mg/0.2 ml/mouse of THG-A once daily during the experiment. The weight gain caused by a high-fat diet was significantly suppressed by oral THG-A compared to a high-fat diet without THG-A. In addition, at eight weeks after starting the diet, the increased plasma total-cholesterol (T-CHO) and low-density lipoprotein-cholesterol (LDL-C) levels caused by a high-fat diet were significantly reduced by 10 mg/mouse THG-A and tended to attenuated by 1 mg/mouse THG-A. The LDL receptor and CYP7A1 mRNA expression in liver associated with lipid metabolism for reducing plasma LDL-C levels was significantly enhanced by oral THG-A. In contrast, oral THG-A exerted no marked effects on mice fed the control diet. The dysbiosis of a high-fat diet fed mice, which is in the form of an increased Firmicutes-to-Bacteroidetes ratio, also recovered, and the high-fat diet induced decreased levels of Bacteroides and Akkermansia genera, which are beneficial microbiota against metabolic disorders, were also restored by oral THG-A. These results indicate that oral THG-A administration acts on metabolic disorders by improving the lipid metabolism and restoring beneficial microbiota to resolve high-fat diet induced dysbiosis. (C) 2020 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

    DOI PubMed

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    3
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  • Thioporidiols A and B: Two New Sulfur Compounds Discovered by Molybdenum-Catalyzed Oxidation Screening from Trichoderma polypori FKI-7382.

    Hirotaka Matsuo, Yoshihiko Noguchi, Rei Miyano, Mayuka Higo, Kenichi Nonaka, Toshiaki Sunazuka, Yōko Takahashi, Satoshi Ōmura, Takuji Nakashima

    Antibiotics (Basel, Switzerland)   9 ( 5 )  2020.05  [Refereed]  [International journal]

    Authorship:Corresponding author

     View Summary

    Two new sulfur compounds, designated thioporidiol A (1) and B (2), were discovered by the MoS-screening program from a culture broth of Trichodermapolypori FKI-7382. The structures of 1 and 2 were determined as C13 lipid structures with an N-acetylcysteine moiety. The relative configuration at the C-5 and C-6 position of 1 was determined by the derivatives of -methoxy--phenylacetic acid diesters, and the absolute configuration of the N-acetylcysteine moiety was determined by advanced Marfey's analysis. Compounds 1 and 2 were evaluated for anti-microbial, cytotoxic and anti-malarial activities. Compound 2 exhibited anti-microbial activity against Candida albicans ATCC 64548.

    DOI PubMed

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  • Actinomycins produced by Streptomyces lichenis LCR6-01T and its antibacterial activity.

    Pawina Kanchanasin, Patcharin Saeng-In, Takuji Nakashima, Hirotaka Matsuo, Yōko Takahashi, Somboon Tanasupawat

    Chiang Mai. J. Sci.   47   864 - 871  2020.05  [Refereed]

  • Trichothioneic acid, a new antioxidant compound produced by the fungal strain Trichoderma virens FKI-7573

    Miyano Rei, Matsuo Hirotaka, Mokudai Takayuki, Noguchi Yoshihiko, Higo Mayuka, Nonaka Kenichi, Niwano Yoshimi, Sunazuka Toshiaki, Shiomi Kazuro, Takahashi Yoko, Omura Satoshi, Nakashima Takuji

    Journal of Bioscience and Bioengineering   129 ( 4 ) 508 - 513  2020.04  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    Trichoderma virens FKI-7573の代謝産物から、奇数の窒素原子を持つ化合物であることを示す奇数分子量ガイド質量分析法を用いて、新規窒素含有化合物のtrichothioneic acid(TA)を見出した。FKI-7573株は北海道帯広市で採取された土壌から単離され、5.8SリボソームRNAを含むITS領域の配列分析により、Trichoderma virensと同定された。TAの構造を質量分析、核磁気共鳴、電子円二色スペクトルと化学分解分析により決定した。その結果、TAはヘプテリジン酸とL-エルゴチオネインから成っており、3つの窒素原子を含んでいた。TCAはヒドロキシルラジカル除去活性とsinglet oxygen消去活性を示した。

    DOI PubMed

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  • Nanaomycin K, a new epithelial-mesenchymal transition inhibitor produced by the actinomycete "Streptomyces rosa subsp. notoensis" OS-3966

    Matsuo Hirotaka, Nakanishi Jun, Noguchi Yoshihiko, Kitagawa Koichi, Shigemura Katsumi, Sunazuka Toshiaki, Takahashi Yoko, Omura Satoshi, Nakashima Takuji

    Journal of Bioscience and Bioengineering   129 ( 3 ) 291 - 295  2020.03  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    新規ナナオマイシン類似体のナナオマイシンKを、放線菌株"Streptomyces rosa subsp. notoensis"OS-3966の培養液から単離した。核磁気共鳴(NMR)分析により、ナナオマイシンKの平面構造にエルゴチオネイン部分が認められた。絶対配置を決定するために、ナナオマイシンKをナナオマイシンEとL-エルゴチオネインの標準品を用いて半合成した。天然および半合成ナナオマイシンKは、保持時間、質量分析、1HNMRおよび旋光度データに基づいて、同じ化合物として同定された。ナナオマイシンKは、トランスフォーミング増殖因子β1により誘発される上皮間葉移行を起こしているMadin-Darbyイヌ腎臓細胞に対して細胞毒性を示した。

    DOI PubMed

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    4
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  • Screening for Sulfur Compounds by Molybdenum-Catalyzed Oxidation Combined with Liquid Chromatography-Mass Spectrometry.

    Hirotaka Matsuo, Takuji Nakashima

    Molecules (Basel, Switzerland)   25 ( 2 )  2020.01  [Refereed]  [Invited]  [International journal]

    Authorship:Corresponding author

     View Summary

    The molybdenum (Mo)-catalyzed oxidation of sulfide under neutral conditions yields sulfone. This reaction proceeds more smoothly than olefin epoxidation and primary or secondary alcohol oxidation. In this study, Mo-catalyzed oxidation was used to screen for sulfur compounds (named "MoS-screening") in microbial broths by liquid chromatography-mass spectrometry (LC/MS). To demonstrate proof-of-concept, known sulfur microbial compounds were successfully identified from a mixture of non-sulfur microbial compounds as sulfinyl or sulfonyl products of Mo-catalyzed oxidation. Then our MoS-screening method was used to screen 300 samples of microbial broth for sulfur compounds. One of the identified compounds was a kitasetaline-containing N-acetyl cysteine moiety produced by an actinomycete strain. These results demonstrate the potential of MoS-screening in the search for new sulfur compounds from microbial sources.

    DOI PubMed J-GLOBAL

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  • Search for new compounds from actinomycete genome using PC screening and their biosynthetic study

    Yuki Inakashi, Takuji Nakashima

    Institute for Fermentation, Osaka. Research Communications   ( 34 )  2020  [Refereed]  [Invited]

    Authorship:Last author, Corresponding author

    J-GLOBAL

  • Search for new compounds using physicochemical screening focused on physicochemical properties of microbial secondary metabolites

    Takuji Nakashima

    Institute for Fermentation, Osaka. Research Communications   ( 34 )  2020  [Refereed]  [Invited]

    Authorship:Lead author, Corresponding author

    J-GLOBAL

  • The search for new compounds by mass spectrometry

    Hirotaka Matsuo, Takuji Nakashima

    Institute for Fermentation, Osaka. Research Communications   ( 34 )  2020  [Refereed]  [Invited]

    Authorship:Corresponding author

    J-GLOBAL

  • The search for new compounds using ergosterol modified silica (ES silica)

    松尾洋孝, 中島琢自

    Institute for Fermentation, Osaka. Research Communications   ( 34 )  2020  [Refereed]  [Invited]

    Authorship:Corresponding author

    J-GLOBAL

  • Screening for nitrogen compounds by principle component analysis with liquid chromatography-mass spectrometry

    松尾洋孝, 中島琢自

    Institute for Fermentation, Osaka. Research Communications   ( 34 )  2020  [Refereed]  [Invited]

    Authorship:Corresponding author

    J-GLOBAL

  • Cipralphelin, a new anti-oxidative N-cinnamoyl tripeptide produced by the deep sea-derived fungal strain Penicillium brevicompactum FKJ-0123

    Matsuo Hirotaka, Mokudai Takayuki, Higo Mayuka, Nonaka Kenichi, Nagano Yuriko, Nagahama Takahiko, Niwano Yoshimi, Takahashi Yoko, Omura Satoshi, Nakashima Takuji

    The Journal of Antibiotics   72 ( 10 ) 775 - 778  2019.10  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    Penicillium brevicompactum FKJ-0123の培養ブロスから、物理化学的スクリーニングにより、新規のN-シンナモイルトリペプチドcipralphelin(I)を単離した。Iの精製にはシリカゲルおよびODSカラムによるクロマトグラフィーを用い、次いで合成的HPLC法を用いた。Iの構造決定には1次元/2次元NMRスペクトル解析法と高分解能質量分析法を中心とした分光分析法を用い、IがN-シンナモイル-プロピル-アラニル-フェニルアラニン・メチルエステルであった。Iを構成する3種類のアミノ酸の絶対構造は、その加水分解物にMarfey法を適用して決定した。Iの細胞毒性、抗菌活性およびスーパーオキシドアニオンラジカルなどの活性酸素種の捕捉能を評価し、Iはヒドロキシラジカルに対して強力な捕捉能を有していた。

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  • Fusaramin, an antimitochondrial compound produced by Fusarium sp., discovered using multidrug-sensitive Saccharomyces cerevisiae

    Sakai Katsuyuki, Unten Yufu, Iwatsuki Masato, Matsuo Hirotaka, Fukasawa Wataru, Hirose Tomoyasu, Chinen Takumi, Nonaka Kenichi, Nakashima Takuji, Sunazuka Toshiaki, Usui Takeo, Murai Masatoshi, Miyoshi Hideto, Asami Yukihiro, Omura Satoshi, Shiomi Kazuro

    The Journal of Antibiotics   72 ( 9 ) 645 - 652  2019.09  [Refereed]  [Domestic journal]

     View Summary

    多剤感受性Saccharomyces cerevisiae 12geneΔ0HSR-iERG6株を用いたバイオアッセイ誘導分画により、Fusarium sp. FKI-7550の培養ブロスから新規化合物fusaramin(I)と共に3種類の既知化合物サンブトキシンとその類似体(II〜IV)を単離した。Iの絶対構造は1次元/2次元NMRスペクトル解析法と円偏光二色性で決定した。Iは数種のグラム陽性/陰性菌に対する抗菌活性を示し、グリセロール含有培地で生育するS.cerevisiae 12geneΔ0HSR-iERG6の増殖を阻害した。グリセロール含有培地で生育する野生型と多剤感受性型の上記酵母に対するMIC値はそれぞれ>128と0.64μg/mLであったが、グルコース含有培地で生育する上記酵母に対するMIC値は>128μg/mLであった。化合物I〜IVはいずれも、単離したS.cerevisiaeミトコンドリアを用いた酸化的リン酸化を経由してATP合成を阻害した。

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  • Sarpeptins A and B, Lipopeptides Produced by Streptomyces sp. KO-7888 Overexpressing a Specific SARP Regulator.

    Wilaiwan Koomsiri, Yuki Inahashi, Kantinan Leetanasaksakul, Kazuro Shiomi, Yo Ko Takahashi, Satoshi O Mura, Markiyan Samborskyy, Peter F Leadlay, Pakorn Wattana-Amorn, Arinthip Thamchaipenet, Takuji Nakashima

    Journal of natural products   82 ( 8 ) 2144 - 2151  2019.08  [Refereed]  [International journal]

    Authorship:Corresponding author

     View Summary

    Whole genome analysis of Streptomyces sp. KO-7888 has revealed various pathway-specific transcriptional regulatory genes associated with silent biosynthetic gene clusters. A Streptomyces antibiotic regulatory protein gene, speR, located adjacent to a novel nonribosomal peptide synthetase (NRPS) gene cluster, was overexpressed in the wild-type strain. The resulting recombinant strain of Streptomyces sp. KO-7888 produced two new lipopeptides, sarpeptins A and B. Their structures were elucidated by high-resolution electrospray ionization mass spectrometry, NMR analysis, and the advanced Marfey's method. The distinct modular sections of the corresponding NRPS biosynthetic gene cluster were characterized, and the assembly line for production of the lipopeptide chain was proposed.

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  • Improvement Effects of Trehangelin A on High-Fat Diet Causing Metabolic Clinical Conditions.

    Hiroki Ishikawa, Satoshi Ino, Takuji Nakashima, Hirotaka Matsuo, Yōko Takahashi, Chikara Kohda, Satoshi Ōmura, Kazuo Tanaka

    Biological & pharmaceutical bulletin   42 ( 12 ) 2095 - 2101  2019  [Refereed]  [Domestic journal]

     View Summary

    The purpose of this study is to determine whether or not trehangelin A (THG-A) is effective in treating the metabolic clinical condition caused by a high-fat diet. The body weight, epididymal adipose volume, alanine transaminase (ALT), total-cholesterol (T-CHO), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and glucose concentrations in serum increased in mice fed a high-fat diet compared to mice fed a control diet. On the other hand, adiponectin level in serum of mice fed a high-fat diet decreased compared to that of control mice. When mice fed a high-fat diet were intraperitoneally administered THG-A of 20 mg/kg three times per week, the levels of TG and glucose in serum were significantly reduced compared to those fed high-fat without THG-A. Interestingly, the levels of high-density lipoprotein cholesterol (HDL-C) in serum were increased by THG-A administration in both mice fed a control diet and those fed high-fat diet. The decreased level of adiponectin by a high-fat diet was also recovered by THG-A treatment. The liver expression of mRNA from pro-inflammatory cytokines, including interleukin (IL)-6 and tumor necrosis factor (TNF)-α, were significantly increased in mice fed a high-fat diet compared to those fed a control diet. However, the increased IL-6 levels in mice fed a high-fat diet were significantly suppressed by THG-A treatment. Furthermore, the increased expression of TNF-α mRNA or COL1A2 mRNA by a high-fat diets tended to be decreased in mice treated with THG-A. These results show that THG-A treatment attenuates the progression of metabolic clinical conditions, suggesting its potential efficacy against obesity-related metabolic disorders.

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  • New tetrahydroquinoline and indoline compounds containing a hydroxy cyclopentenone, virantmycin B and C, produced by Streptomyces sp. AM-2504.

    Kimura, T, Suga, T, Kameoka, M, Ueno, M, Inahashi, Y, Matsuo, H, Iwatsuki, M, Shigemura, K, Shiomi, K, Takahashi, Y, Ōmura, S, Nakashima, T

    The Journal of antibiotics   72 ( 3 ) 169 - 173  2018.12  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    Two new antibiotics, designated virantmycin B (1) and C (2), were isolated from the cultured broth of Streptomyces sp. AM-2504. Compounds 1 and 2 were purified by Diaion HP-20, silica gel, and octadecylsilane chromatography, followed by high-performance liquid chromatography. The chemical structures of the new compounds, 1 and 2, were determined by nuclear magnetic resonance and mass spectrometry, as containing a terahydroquinoline and an indoline, respectively, each also containing a hydroxy cyclopentenone moiety. Both compounds demonstrated weak antimicrobial (both antibacterial and antifungal) activity and compound 1 also showed antiviral activity against the dengue virus, whereas compound 2 exhibited no antiviral properties.

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  • Nanaomycin I and J: New nanaomycins generated by mycothiol-mediated compounds from "Streptomyces rosa subsp. notoensis" OS-3966.

    Matsuo, H, Noguchi, Y, Také, A, Nakanishi, J, Shigemura, K, Sunazuka, T, Takahashi, Y, Ōmura, S, Nakashima, T

    Journal of bioscience and bioengineering   127 ( 5 ) 549 - 553  2018.11  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    Two new nanaomycin analogs, nanaomycin I and J, were isolated from a cultured broth of an actinomycete strain, "Streptomyces rosa subsp. notoensis" OS-3966. In our previous study, we have confirmed the occurrence of nanaomycin I (m/z = 482 [M + H]+) that lacks a pseudo-disaccharide from the mycothiol of nanaomycin H under same culture condition. In this study, to confirm the structure of nanaomycin I, the strain "S. rosa subsp. notoensis" OS-3966 was re-cultured and the target compound with m/z = 482 [M + H]+ was isolated. Furthermore, we discovered another new analog, designated as nanaomycin J in isolating nanaomycin I. The NMR analyses revealed that the structures of nanaomycin I and J are N-acetylcysteine S-conjugates without a pseudo-disaccharide and N-acetylcysteine S-conjugates without a myo-inositol of nanaomycin H, respectively. The relative configurations of the tetrahydropyrane moiety of nanaomycin I and J were determined by rotating-frame overhauser effect spectroscopy (ROESY) analysis. Absolute configurations of the N-acetylcysteine moiety of nanaomycin I and J were determined by advanced Marfey's analyses for acid hydrolysis of de-sulfurized nanaomycin I and J with Raney nickel. Nanaomycin I and J showed moderate cytotoxicity against several human tumor cell lines.

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  • An Application of Photoactivatable Substrate for the Evaluation of Epithelial-mesenchymal Transition Inhibitors.

    Nakanishi, J, Sugiyama, K, Matsuo, H, Takahashi, Y, Mura, S.O, Nakashima, T

    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry   35 ( 1 ) 65 - 69  2018.11  [Refereed]  [Domestic journal]

     View Summary

    Epithelial-mesenchymal transition (EMT), phenotypic changes in cell adhesion and migration, is involved in cancer invasion and metastasis, hence becoming a target for anti-cancer drugs. In this study, we report a method for the evaluation of EMT inhibitors by using a photoactivatable gold substrate, which changes from non-cell-adhesive to cell-adhesive in response to light. The method is based on the geometrical confinement of cell clusters and the subsequent migration induction by controlled photoirradiation of the substrate. As a proof-of-concept experiment, a known EMT inhibitor was successfully evaluated in terms of the changes in cluster area or leader cell appearance, in response to biochemically and mechanically induced EMT. Furthermore, an application of the present method for microbial secondary metabolites identified nanaomycin H as an EMT inhibitor, potentially killing EMTed cells in disseminated conditions. These results demonstrate the potential of the present method for screening new EMT inhibitors.

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  • Pochoniolides A and B, new antioxidants from the fungal strain Pochonia chlamydosporia var. spinulospora FKI-7537.

    Rei Miyano, Hirotaka Matsuo, Kenichi Nonaka, Takayuki Mokudai, Yoshimi Niwano, Kazuro Shiomi, Yōko Takahashi, Satoshi Ōmura, Takuji Nakashima

    Journal of bioscience and bioengineering   126 ( 5 ) 661 - 666  2018.11  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    New natural products, designated pochoniolides A and B, were isolated from the cultured broth of fungal strain FKI-7537 using a physicochemical screening methodology. Strain FKI-7537 was isolated from a soil sample collected at Niijima, Tokyo, Japan and identified as Pochonia chlamydosporia var. spinulospora by morphological characteristics and DNA sequence analysis. The chemical structures of pochoniolides A and B were elucidated by NMR and mass spectra and found to be new compounds consisting of a muconolactone moiety connected with a chromone unit. Pochoniolides A and B were identified as racemate mixtures using data on optical rotation and circular dichroism spectra. Furthermore, enantiomers of pochoniolide B, pochoniolides B1 and B2, were separated using a chiral HPLC column. Pochoniolides A and B showed hydroxyl radical-scavenging and singlet oxygen-quenching activities.

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  • A novel pathway for the photooxidation of catechin in relation to its prooxidative activity.

    Shishido, S, Miyano, R, Nakashima, T, Matsuo, H, Iwatsuki, M, Nakamura, K, Kanno, T, Egusa H, Niwano, Y

    Scientific reports   8 ( 1 ) 12888 - 12888  2018.08  [Refereed]  [International journal]

     View Summary

    In the present study, we evaluated the prooxidative mode of action of photoirradiated (+)-catechin at 400 nm in relation to reactive oxygen species generation and its possible application to disinfection. Photoirradiation of (+)-catechin at a concentration of 1 mg/mL yielded not only hydrogen peroxide (H2O2) but hydroxyl radical (·OH) in a total amount of approximately 20 μM in 10 min. As a result, photoirradiated catechin killed Staphylococcus aureus, and a > 5-log reduction in viable bacteria counts was observed within 20 min. Liquid chromatography-high-resolution-electrospray ionization-mass spectrometry showed that photoirradiation decreased the (+)-catechin peak (molecular formula C15H14O6) whilst it increased two peaks of a substance with the molecular formula C15H12O6 with increasing irradiation time. Nuclear magnetic resonance analysis revealed that the two C15H12O6 peaks were allocated to intramolecular cyclization products that are enantiomers of each other. These results suggest that photoirradiation induces oxidation of (+)-catechin resulting in the reduction of oxygen to generate H2O2. This H2O2 is then homolytically cleaved to ·OH, and alongside this process, (+)-catechin is finally converted to two intramolecular cyclization products that are different from the quinone structure of the B ring, as proposed previously for the autoxidation and enzymatic oxidation of catechins.

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  • Pestynol, an Antifungal Compound Discovered Using a Saccharomyces cerevisiae 12geneΔ0HSR-iERG6-Based Assay.

    Sakai, K, Hirose, T, Iwatsuki, M, Chinen, T, Kimura, T, Suga, T, Nonaka, K, Nakashima, T, Sunazuka, T, Usui, T, Asami, Y, Ōmura, S, Shiomi, K

    Journal of natural products   81 ( 7 ) 1604 - 1609  2018.07  [Refereed]  [International journal]

     View Summary

    The multidrug-sensitive budding yeast, Saccharomyces cerevisiae 12geneΔ0HSR-iERG6, is very useful in antifungal screens. A novel compound, named pestynol (1), was discovered from a culture of the fungus Pestalotiopsis humus FKI-7473 using the multidrug-sensitive yeast. The structure of 1 was elucidated by NMR studies and modified Mosher's method as (1 R,2 R,3 R,4 R)-( E)-5-(7,11-dimethyl-3-methylenedodeca-6,10-dien-1-yn-1-yl)cyclohex-5-ene-1,2,3,4-tetraol. Compound 1 showed antimicrobial activity against the Gram-positive bacteria, Klebsiella pneumoniae, and S. cerevisiae 12geneΔ0HSR-iERG6 and Mucor racemosus, but displayed only weak cytotoxicity against various human cancer cell lines. Compound 1 displayed antifungal activities against S. cerevisiae 12geneΔ0HSR-iERG6 and Mucor racemosus at 10 μg/disc.

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  • Microorganisms are an inexhaustible gold mine of new natural compounds

    The Japanese Journal of Antibiotics   71 ( 3 ) 99 - 112  2018.06  [Refereed]

  • Actinomycetes, an Inexhaustible Source of Naturally Occurring Antibiotics

    Takuji Nakashima, Yoko Takahashi, Ōmura Satoshi

    Antibiotics   7 ( 2 )  2018.05  [Refereed]  [Invited]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Global public health faces a desperate situation, due to the lack of effective antibiotics. Coordinated steps need to be taken, worldwide, to rectify this situation and protect the advances in modern medicine made over the last 100 years. Work at Japan's Kitasato Institute has been in the vanguard of many such advances, and work is being proactively tailored to promote the discovery of urgently needed antimicrobials. Efforts are being concentrated on actinomycetes, the proven source of most modern antibiotics. We devised a novel physicochemical screening mechanism, whereby simple physico-chemical properties, in conjunction with related detection methods, such as LC/MS, LC/UV, and polarity, could be used to identify or predict new compounds in a culture broth, simply by comparing results with existing databases. New compounds are isolated, purified, and their structure determined before being tested for any bioactivity. We used lyophilized actinomycete strains from the Kitasato Microbial Library, most more than 35 years old, and found 330 strains were producers of useful bioactive substances. We also tested organisms found in fresh samples collected in the complex environments from around plant roots, as well as from sediments of mangrove forests and oceans, resulting in the discovery of 36 novel compounds from 11 actinomycete strains. A compound, designated iminimycin, containing an iminium ion in the structure was discovered from the culture broth of Streptomyces griseus OS-3601, which had been stored for a long time as a streptomycin-producing strain. This represented the first iminium ion discovery in actinomycetes. Compounds with a cyclopentadecane skeleton containing 5,6-dihydro-4-hydroxyl-2-pyrone ring and tetrahydrofuran ring, designated mangromicins, were isolated from the culture broth of Lechevalieria aerocolonigenes K10-0216 obtained from sediment in a mangrove forest. These structures are extremely unique among natural compounds. From the same culture broth, new steroid compounds, named K10-0216 KA and KB, and other new compounds having a thiazole and a pyridine ring, named pyrizomicin A and B, were discovered. New substances can be found from actinomycetes that have been exhaustively studied. Novel compounds with different skeletons can be found from a single broth of one strain. The sought after new antibiotics will arise from continued exploitation of the actinomycetes, especially rare actinomycetes. Work on new organisms and samples should be augmented by re-examination of known actinomycetes already in storage. New research should also be carried out on the manipulation of culture media, thereby stimulating actinomycete strains to produce novel chemicals. The establishment of wide-ranging international research collaborations will facilitate and expedite the efficient and timely discovery and provision of bioactive compounds to help maintain and promote advances in global public health.

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  • New metabolites, sarcopodinols A and B, isolated from deep-sea derived fungal strain Sarcopodium sp. FKJ-0025.

    Matsuo, H, Nonaka, K, Nagano, Y, Yabuki, A, Fujikura, K, Takahashi, Y, Ōmura, S, Nakashima, T

    Bioscience, biotechnology, and biochemistry   82 ( 8 ) 1323 - 1326  2018.04  [Refereed]  [International journal]

    Authorship:Corresponding author

     View Summary

    Fungal strain FKJ-0025 was isolated from deep-sea sediment collected at the Wakamiko Caldera in Kagoshima Bay (water depth: 200 m). The fungal strain FKJ-0025 was identified as the genus Sarcopodium based on its morphology and internal transcribed spacer (ITS) sequence. Two new compounds, designated sarcopodinols A (1) and B (2), were isolated together with the known compound SF-227 (3).

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  • Hamuramicins A and B, 22-membered macrolides, produced by an endophytic actinomycete Allostreptomyces sp. K12-0794.

    Kimura, T, Inahashi, Y, Iwatsuki, M, Nonaka, K, Také, A, Matsumoto, A, Takahashi, Y, Ōmura, S, Nakashima, T

    The Journal of antibiotics   71 ( 7 ) 619 - 625  2018.04  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    Two new compounds, designated as hamuramicins A (1) and B (2), were isolated from the cultured broth of an endophytic actinomycete Allostreptomyces sp. K12-0794 by silica gel column chromatography and HPLC. The structures of 1 and 2 were elucidated as 22-membered macrolide containing triene and trienone with an alkyl side chain by spectroscopic analyses including NMR experiments. Both compounds showed growth inhibition activity against Kocuria rhizophia and Xanthomonas oryzae pv. oryzae as well as human cell line toxicity.

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  • Identification and heterologous expression of the actinoallolide biosynthetic gene cluster.

    Inahashi, Y, Shiraishi, T, Také, A, Matsumoto, A, Takahashi, Y, Ōmura, S, Kuzuyama, T, Nakashima, T

    The Journal of antibiotics   71 ( 8 ) 749 - 752  2018.04  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    Actinoallolides are anti-trypanosomal macrolides isolated from the secondary metabolites of two endophytic actinomycete strains, Actinoallomurus fulvus MK10-036 and K09-0307. A putative actinoallolide biosynthetic gene cluster was predicted from the genome sequence of the strain K09-0307. The gene cluster spans a contiguous 53 kb DNA region that comprises seven genes encoding three PKSs (aalA1, aalA2, and aalA3), cytochrome P450 (aalB), acyl-CoA dehydrogenase (aalC), crotonyl-CoA reductase (aalD), and TetR family regulator (aalR). The entire gene cluster was cloned into a plasmid pYIK1 by assembling DNA fragments, which were obtained from two cosmids containing left and right parts of the gene cluster. Following the introduction of an ermE* promoter at 100bp upstream from the start codon of aalA1, the gene cluster was introduced into Streptomyces coelicolor M1152. Subsequent LC-MS analysis revealed production of actinoallolide A in the culture broth. Thus, the actinoallolide biosynthetic gene cluster was identified by heterologous expression in Streptomyces.

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  • Pyrizomicin A and B: structure and bioactivity of new thiazolyl pyridines from Lechevalieria aerocolonigenes K10-0216.

    Kimura, T, Inahashi, Y, Matsuo, H, Suga, T, Iwatsuki, M, Shiomi, K, Takahashi, Y, Ōmura, S, Nakashima, T

    The Journal of antibiotics   71 ( 6 ) 606 - 608  2018.03  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    Two new antibiotics, designated pyrizomicin A and B, were isolated from the cultured broth of a rare actinomycete strain, Lechevalieria aerocolonigenes K10-0216, by silica gel and HPLC purification. The chemical structures of pyrizomicin A and B were elucidated as new thiazolyl pyridine compounds by nuclear magnetic resonance and mass spectrometry. Pyrizomicin A and B both showed antimicrobial activity.

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  • Dipyrimicin A and B, microbial compounds isolated from Amycolatopsis sp. K16-0194.

    Izuta, S, Kosaka, S, Kawai, M, Miyano, R, Matsuo, H, Matsumoto, A, Nonaka, K, Takahashi, Y, Ōmura, S, Nakashima, T

    The Journal of antibiotics   71 ( 5 ) 535 - 537  2018.02  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    In a search for compounds interacting with ergosterol resin, a new compound named dipyrimicin B was isolated from a rare actinomycete strain, Amycolatopsis sp. K16-0194. In addition, another analog, dipyrimicin A, which does not interact with the resin, was also discovered. The structures of the two dipyrimicins were established by comprehensive 1D and 2D NMR and MS analyses and found to contain a unique core structure, a 2,2'-bipyridine skeleton. Dipyrimicin A showed strong antimicrobial and cytotoxic activity, whereas dipyrimicin B displayed distinctly poor antimicrobial and cytotoxic activities.

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  • Mumiamicin: Structure and bioactivity of a new furan fatty acid from Mumia sp. YSP-2-79.

    Kimura, T, Tajima, A, Inahashi, Y, Iwatsuki, M, Kasai, H, Mokudai, T, Niwano, Y, Shiomi, K, Takahashi, Y, Ōmura, S, Nakashima, T

    The Journal of general and applied microbiology   64 ( 2 ) 62 - 67  2018.01  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    A new antibiotic, designated mumiamicin, was isolated from the cultured broth of the rare actinomycete strain, Mumia sp. YSP-2-79, by Diaion HP-20, silica gel and ODS column chromatography, followed by HPLC purification. The chemical structure of mumiamicin was elucidated as a new furan fatty acid by nuclear magnetic resonance and mass spectrometry. Mumiamicin showed antimicrobial activity and antioxidative activity.

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  • Jietacins, azoxy antibiotics with potent nematocidal activity: Design, synthesis, and biological evaluation against parasitic nematodes.

    Sugawara, A, Kubo, M, Hirose, T, Yahagi, K, Tsunoda, N, Noguchi, Y, Nakashima, T, Takahashi, Y, Welz, C, Mueller, D, Mertens, C, Koebberling, J, Ōmura, S, Sunazuka, T

    European journal of medicinal chemistry   145   524 - 538  2017.12  [Refereed]  [International journal]

     View Summary

    Jietacins, an azoxy antibiotic class of chemicals, were isolated from the culture broth of Streptomyces sp. KP-197. They have a unique structural motif, including a vinyl azoxy group and a long acyclic aliphatic chain, which is usually branched but non-branched in the case of jietacin C. During a drug discovery program, we found that jietacins display potent anthelmintic activity against parasitic nematodes and that jietacin A has a moderate or low acute toxicity (LD50 > 300 mg/kg) and no mutagenic potential in a mini Ames screen. This suggests that jietacins have potential for drug discovery research. In order to create a novel anthelmintic agent, we performed design, synthesis, and biological evaluation of jietacin derivatives against parasitic nematodes. Of these derivatives, we found that a fully synthesized simplified derivative exhibited better anthelmintic activity against three parasitic nematodes than natural jietacins. In addition, it had a better efficacy in vivo through oral administration against a mouse nematode. This indicated that the azoxy motif could prove useful as a template for anthelmintic discovery, possibly creating a class of anthelmintic with novel skeletons, a potential new mode of action, and providing further insight for rational drug design.

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  • Bisoxazolomycin A: a new natural product from 'Streptomyces subflavus subsp. irumaensis' AM-3603.

    Koomsiri, W, Inahashi, Y, Kimura, T, Shiomi, K, Takahashi, Y, Omura, S, Thamchaipenet, A, Nakashima, T

    The Journal of antibiotics   70 ( 12 ) 1142 - 1145  2017.09  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    Bisoxazolomycin (1), oxazolomycin A2 (2) and oxazolomycin A (3) were identified by physicochemical screening approach from a culture broth of 'Streptomyces subflavus subsp. irumaensis' AM-3603. Compound 2 is a hydrolyzed analog of 3 at the β-lactone ring, and 1 is a new dimeric analog of 2. Compounds 1 and 2 exhibited less potent antibacterial activity and cytotoxicity than 3, which might be due to lack of the β-lactone ring.

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  • Search for new compounds from Kitasato microbial library by physicochemical screening.

    Takuji Nakashima, Yōko Takahashi, Satoshi Ōmura

    Biochemical pharmacology   134   42 - 55  2017.06  [Refereed]  [Invited]  [International journal]

     View Summary

    The Ōmura research group of the Kitasato Institute has isolated multiple microorganisms over a period of five decades. The resulting collection comprises a broad spectrum of microbes, including strains producing novel and diverse compounds with biological activities. A bioassay-guided fractionation of microbial culture broths has been employed to screen the microbial collection for compounds with new biological activities. And numerous novel natural products have been discovered among the microbial metabolites produced by members of the collection. However, dereplication of already known compounds and their potential analogs is a vital part of the discovery process of new microbial natural products. Recently, it has become easy to acquire the ultraviolet (UV) and mass spectrometry (MS) spectra of many single components of microbial culture broths in combination with high-performance liquid chromatography. To achieve most effective utilization of our microbial library, new compounds from microbial culture broths were investigated by employing an approach based on the physico-chemical properties using spectral analyses such as UV and MS and color reaction, collectively designated as physicochemical (PC) screening. As a result of physicochemical screening, many new compounds were identified among the secondary metabolites of fresh isolated rare actinomycetes and Streptomyces spp. preserved for a long time as producer of biological compounds. In this review, we introduce the Kitasato microbial library and the new compounds discovered from the library by PC screening.

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  • Nanaomycin H: A new nanaomycin analog.

    Nakashima, T, Kimura, T, Miyano, R, Matsuo, H, Hirose, T, Kimishima, A, Nonaka, K, Iwatsuki, M, Nakanishi, J, Takahashi, Y, Ōmura, S

    Journal of bioscience and bioengineering   123 ( 6 ) 765 - 770  2017.02  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Physicochemical screening identified a new nanaomycin analog, nanaomycin H, which was isolated from a culture broth of Streptomyces rosa subsp. notoensis OS-3966. This microorganism is already known to produce seven nanaomycin compounds, (nanaomycin A to G). Structural elucidation of nanaomycin H showed it to be a pyranonaphthoquinone with a mycothiol moiety. A N-acetylcysteine S-conjugate of nanaomycin H, without α-glucosamine linked to myo-inositol moiety, mercapturic acid derivative, was also detected in the same culture broth. Mercapturic acid derivatives of secondary metabolites are known to be produced for xenobiotic metabolism outside microbial cells. Mycothiol acts as a detoxifier to help prevent cell damage from factors such as oxidative stress. The production of O2- generated by reduction of nanaomycin A is correlated with antibacterial activity. Mycothiol-containing nanaomycin H proved to be markedly decreased in O2- and did not express any notable antimicrobial activity. It is suggested that nanaomycin H is produced in the detoxification process.

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  • Decatamariic acid, a new mitochondrial respiration inhibitor discovered by pesticidal screening using drug-sensitive Saccharomyces cerevisiae.

    Watanabe, Y, Suga, T, Narusawa, S, Iwatsuki, M, Nonaka, K, Nakashima, T, Shinohara, Y, Shiotsuki, T, Ichimaru, N, Miyoshi, H, Asami, Y, Shiomi, K

    The Journal of antibiotics   70 ( 4 ) 395 - 399  2017.01  [Refereed]  [Domestic journal]

     View Summary

    A new decalin, decatamariic acid, was isolated from a cultured broth of the fungus Aspergillus tamarii FKI-6817. Its absolute configuration was elucidated by NMR and electronic circular dichroism. Decatamariic acid (10 μM) elicited ~50% inhibition of the ATP production in mitochondria isolated from wild-type Saccharomyces cerevisiae without affecting the activities of respiratory enzymes. The action manner of this compound may be interesting as a possible seed for new pesticides.

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    4
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  • Diversity of Endophytic Actinomycetes Isolated from Roots and Root Nodules of Pueraria candollei Grah. ex Benth. and the Analyses of Their Secondary Metabolites

    Panitch Boonsnongcheep, Takuji Nakashima, Yoko Takahashi, Sompop Prathanturarug

    CHIANG MAI JOURNAL OF SCIENCE   44 ( 1 )  2017.01  [Refereed]

     View Summary

    Pueraria candollei Grah. ex Benth. is a Thai herb that contributes to many phytoestrogenic-related pharmacological activities. In this study, the diversity of endophytic actinomycetes from roots and root nodules of P. candollei and actinomycetes from rhizospheric soils were investigated. Moreover, the secondary metabolites production of these isolated actinomycetes was investigated. A total of 85 isolates were obtained from roots, root nodules and rhizospheric soils, 32 from the roots of P. candollei var. candollei, 26 from the root nodules of P. candollei var. mirifica and 27 from rhizospheric soil samples. Partial 16S rRNA sequence data revealed that the isolated actinomycetes were distributed among 7 genera including, Streptomyces, Micromonospora, Verrucosispora, Microbispora, Nonomuraea, Plantactinospora and Shimazuella. The majority of isolates from plant sources were members of the genus Micromonospora. Broth extracts of these isolates were analyzed using LC/UV and LC/MS. The physicochemical properties of 10 selected peaks were searched in the database. The physicochemical properties of some peaks were matched with known microbial metabolites. The structure of an unknown compound was elucidated using spectroscopic data. The NMR data indicated the presence of N-acetylhomocysteine moiety and the compound was determined to be S-adenosyl-N-acetylhomocysteine. This compound was isolated from Micromonospora for the first time. In conclusion, this work contributed to the known information on the diversity of actinomycetes associated with P. candollei and their capability for secondary metabolite production.

  • Total Synthesis and Determination of the Absolute Configuration of Naturally Occurring Mangromicin A, with Potent Antitrypanosomal Activity.

    Takada, H, Yamada, T, Hirose, T, Ishihara, T, Nakashima, T, Takahashi, Y, Ōmura, S, Sunazuka, T

    Organic letters   19 ( 1 ) 230 - 233  2016.12  [Refereed]  [International journal]

     View Summary

    An enantioselective total synthesis of (+)-mangromicin A has been accomplished. The tetrahydrofuran ring of mangromicin A, possessing a tetrasubstituted carbon center, was constructed by Mukaiyama-type vinylogous alkylation via a cyclic oxocarbenium intermediate derived from a γ-hydroxy ketone with ideal stereoselectivity, and the 4-hydroxydihydropyrone scaffold was generated via Dieckmann cyclization at a late stage of the total synthesis. The reliable asymmetric synthesis of (+)-mangromicin A has revealed the absolute configuration of naturally occurring mangromicin A.

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  • Anti-trypanosomal compound, sagamilactam, a new polyene macrocyclic lactam from Actinomadura sp. K13-0306.

    Tōru Kimura, Masato Iwatsuki, Yukihiro Asami, Aki Ishiyama, Rei Hokari, Kazuhiko Otoguro, Atsuko Matsumoto, Noriko Sato, Kazuro Shiomi, Yōko Takahashi, Satoshi Ōmura, Takuji Nakashima

    The Journal of antibiotics   69 ( 11 ) 818 - 824  2016.11  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    A new antibiotic, designated sagamilactam, was isolated from the cultured broth of Actinomadura sp. K13-0306 by Diaion HP-20, silica gel and octadecylsilane column chromatography followed by purification by HPLC. The chemical structure of the new compound was elucidated by spectroscopic analyses, including NMR and MS. The structure of sagamilactam proved to be a new compound consisting of a polyunsaturated and polyoxygenated 34-membered macrocyclic lactam containing diene, triene and tetraene conjugated olefins and a decalin moiety. Sagamilactam showed antitrypanosomal activity with an IC50 value of 0.25±0.11 μM.

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  • Analyses of the cell-wall peptidoglycan structures in three genera Micromonospora, Catenuloplanes, and Couchioplanes belonging to the family Micromonosporaceae by derivatization with FDLA and PMP using LC/MS.

    Akira Také, Takuji Nakashima, Yuki Inahashi, Kazuro Shiomi, Yōko Takahashi, Satoshi Ōmura, Atsuko Matsumoto

    The Journal of general and applied microbiology   62 ( 4 ) 199 - 205  2016.09  [Refereed]  [Domestic journal]

     View Summary

    It is the major characteristic of the cell-wall peptidoglycan structure in members of the family Micromonosporaceae that N-acetylmuramic acid (MurNAc) of glycan strand is replaced with N-glycolylmuramic acid (MurNGlyc). Consequently, it is difficult to use enzymatic methods for their peptidoglycan analyses. We therefore developed analysis method of peptidoglycan without using cell wall lytic enzymes as example to take the 3 genera, Micromonospora, Catenuloplanes, and Couchioplanes belonging to the family Micromonosporaceae, and their peptidoglycans were partially hydrolyzed with 4 M HCl at 60°C for 16 h followed by derivatization with N(α)-(5-fluoro-2,4-dinitrophenyl)-D-leucinamide (FDLA) or 1-phenyl-3-methyl-5-pyrazolone (PMP) and LC/MS analysis. Peptidoglycan of the genus Micromonospora consisted of a MurNGlyc-Gly-D-Glu-meso-diaminopimelyl (DAP)-D-Ala peptide stem and direct linkage between D-Ala and meso-DAP. In contrast, peptidoglycans of the genera Catenuloplanes and Couchioplanes consisted of a MurNGlyc-Gly-D-Glu-L-Lys-D-Ala peptide stem, and cross-linkage between D-Ala and L-Lys was mediated by an L-Ser residue. This method can be used to analyze the cell-wall peptidoglycan structure of other bacteria as well. By derivatization with FDLA or PMP followed by LC/MS analysis, the structure can be determined using only 0.2 mg of purified peptidoglycan.

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  • Biosynthesis of Trehangelin in Polymorphospora rubra K07-0510: Identification of Metabolic Pathway to Angelyl-CoA.

    Yuki Inahashi, Taro Shiraishi, Kaia Palm, Yoko Takahashi, Satoshi Ōmura, Tomohisa Kuzuyama, Takuji Nakashima

    Chembiochem : a European journal of chemical biology   17 ( 15 ) 1442 - 7  2016.08  [Refereed]  [International journal]

    Authorship:Corresponding author

     View Summary

    Trehangelins are trehalose angelates discovered from endophytic actinomycete Polymorphospora rubra K07-0510. We identified the trehangelin biosynthetic gene cluster, including genes that encode a glycoside hydrolase-like protein (thgC), α-amylase (thgD), 3-ketoacyl-ACP synthase III (thgI), 3-ketoacyl-ACP reductase (thgK), enoyl-CoA hydratase (thgH) and acyl transferase (thgJ). Heterologous expression of thgH, thgI, thgJ and thgK confirmed the importance of these genes in the biosynthesis of trehangelin A. Enzymatic activity studies showed that ThgI catalyses the condensation of acetyl-CoA and methylmalonyl-CoA to 2-methylacetoacetyl-CoA (MAA-CoA), ThgK catalyses NADPH-dependent reduction of MAA-CoA to 3-hydroxy-2-methylbutyryl-CoA (HMB-CoA) and ThgH catalyses the dehydration of HMB-CoA to angelyl-CoA (AN-CoA). This is the first report on the elucidation of the enzymatic formation of AN-CoA.

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  • Iminimycin A, the new iminium metabolite produced by Streptomyces griseus OS-3601.

    Takuji Nakashima, Rei Miyano, Masato Iwatsuki, Tatsuya Shirahata, Toru Kimura, Yukihiro Asami, Yoshinori Kobayashi, Kazuro Shiomi, George A Petersson, Yōko Takahashi, Satoshi Ōmura

    The Journal of antibiotics   69 ( 8 ) 611 - 5  2016.08  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

     View Summary

    A new natural product, designated iminimycin A, was isolated from the cultured broth of a streptomycin-producing microbial strain, Streptomyces griseus OS-3601, via a physicochemical screening method using HP-20, silica gel and ODS column chromatographies and subsequent preparative HPLC. Iminimycin A is an indolizidine alkaloid, containing of an unusual iminium group and a cyclopropane ring with a triene side chain. The absolute configuration of iminimycin A was elucidated by NMR studies and electronic circular dichroism analysis. Iminimycin A shows anti-bacterial activity against Bacillus subtilis, Kocuria rhizophila and Xanthomonas campestris pv. orizae, and cytotoxic activity against HeLa S3 and Jurkat cells with IC50 values of 43 and 36 μM, respectively.

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  • Absolute configuration of iminimycin B, a new indolizidine alkaloid, from Streptomyces griseus OS-3601

    Takuji Nakashima, Rei Miyano, Hirotaka Matsuo, Masato Iwatsuki, Tatsuya Shirahata, Yoshinori Kobayashi, Kazuro Shiomi, George A. Petersson, Yoko Takahashi, Satoshi Omura

    TETRAHEDRON LETTERS   57 ( 30 ) 3284 - 3286  2016.07  [Refereed]

    Authorship:Lead author, Corresponding author

     View Summary

    Iminimycin B, a novel indolizine alkaloid featuring a rare pyridinium, was isolated from the cultured broth of a streptomycin-producing strain, Streptomyces griseus OS-3601, through a physicochemical screening method. Its structure was elucidated on the basis of mass and NMR analyses. Stereochemical assignment of iminimycin B was archived by NMR studies, electronic circular dichroism (ECD) analysis, and advanced Marfey's method. (C) 2016 Elsevier Ltd. All rights reserved.

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  • Prooxidative Potential of Photo-Irradiated Aqueous Extracts of Grape Pomace, a Recyclable Resource from Winemaking Process.

    Mana Tsukada, Takuji Nakashima, Toshiaki Kamachi, Yoshimi Niwano

    PloS one   11 ( 6 ) e0158197  2016  [Refereed]  [International journal]

     View Summary

    Our previous study revealed that aqueous extract of grape pomace obtained from a winemaking process could exert bactericidal action upon photo-irradiation via reactive oxygen species (ROS) formation. In the present study, we focused on chemical composition and prooxidative profile of the extract. Liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analysis showed that polyphenolic compounds including catechin monomers, dimers, trimers, and polyphenolic glucosides were contained. The polyphenol rich fraction used for the LC-ESI-MS analysis generated hydrogen peroxide (H2O2) upon photo-irradiation possibly initiated by photo-oxidation of phenolic hydroxyl group. That is, reduction of dissolved oxygen by proton-coupled electron transferred from the photo-oxidized phenolic hydroxyl group would form H2O2. The resultant H2O2 was then photolyzed to generate hydroxyl radical (•OH). The prooxidative profile of the extract in terms of •OH generation pattern upon photo-irradiation was similar to that of grape seed extract (GSE) as an authentic polyphenol product and (+)-catechin as a pure polyphenolic compound, and in all the three samples •OH generation could be retained during photo-irradiation for at least a couple of hours. The prooxidant activity of the photo-irradiated extract indicated by •OH yield was more potent than that of the photo-irradiated GSE and (+)-catechin, and this was well reflected in their bactericidal activity in which the photo-irradiated extract could kill the bacteria more efficiently than did the photo-irradiated GSE and (+)-catechin.

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  • New compounds, nanaomycin F and G, discovered by physicochemical screening from a culture broth of Streptomyces rosa subsp. notoensis OS-3966.

    Takuji Nakashima, Panitch Boonsnongcheep, Toru Kimura, Masato Iwatsuki, Noriko Sato, Kenichi Nonaka, Sompop Prathanturarug, Yōko Takahashi, Satoshi Ōmura

    Journal of bioscience and bioengineering   120 ( 5 ) 596 - 600  2015.11  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Two new compounds, nanaomycin F and G, were isolated by physicochemical screening method from cultured broth of Streptomyces rosa subsp. notoensis OS-3966, which is known to produce nanaomycin A, B, C, D, and E. Nanaomycin F is a new nanaomycin analog, a 4a-hydroxyl analog of nanaomycin B. Nanaomycin G has a unique skeleton with 1-indanone infused with a tetrahydropyran ring. Nanaomycin A possesses broad antimicrobial activity but nanaomycin F and G demonstrated no bioactivity against all bacteria and fungi tested in this study. In addition, in both nanaomycin F and G, the production of superoxide radicals was majorly decreased in comparison to nanaomycin A. It was considered that the antimicrobial properties were lost as a result of the decrease in production of the superoxide radicals.

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  • Ascosteroside C, a new mitochondrial respiration inhibitor discovered by pesticidal screening using recombinant Saccharomyces cerevisiae.

    Takuya Suga, Yukihiro Asami, Shohei Hashimoto, Kenichi Nonaka, Masato Iwatsuki, Takuji Nakashima, Ryohei Sugahara, Takahiro Shiotsuki, Takenori Yamamoto, Yasuo Shinohara, Naoya Ichimaru, Masatoshi Murai, Hideto Miyoshi, Satoshi Ōmura, Kazuro Shiomi

    The Journal of antibiotics   68 ( 10 ) 649 - 52  2015.10  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

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  • New steroidal compounds from an actinomycete strain, Lechevalieria aerocolonigenes K10-0216.

    Takuji Nakashima, Yoshiyuki Kamiya, Kenzaburo Yamaji, Masato Iwatsuki, Noriko Sato, Yōko Takahashi, Satoshi Ōmura

    The Journal of antibiotics   68 ( 5 ) 348 - 50  2015.05  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

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  • Jietacins with potent nematocidal activity; efficient isolation of novel analogs and divergent total synthesis of jietacin A, B, C, and D

    Akihiro Sugawara, Masahiko Kubo, Takuji Nakashima, Tomoyasu Hirose, Noriaki Tsunoda, Kyoichi Yahagi, Yukihiro Asami, Takeshi Yamada, Kazuro Shiomi, Yoko Takahashi, Satoshi Omura, Toshiaki Sunazuka

    TETRAHEDRON   71 ( 14 ) 2149 - 2157  2015.04  [Refereed]

     View Summary

    Jietacin compounds are known to display potent nematocidal activity being 10-fold more active against the pine wood nematode (Bursaphelenchus lignicolus) than avermectin B1a. They consist of a unique functional vinylazoxy group. Herein, we disclose not only the isolation of novel analogs (jietacin C and D) but also a divergent and a 7-step total synthesis for jietacin A, B, C, and (S and R) D in 30-36% overall yield, incorporating reductive hydrazination, regioselective azoxy formation, and C C bond formation via acylation using Grignard reagents in the presence of vinylazoxy moiety at the final stage. In addition, we evaluated the nematocidal activity of jietacin A D and synthetic intermediates against Caenorhabditis elegans as a model nematode. (C) 2015 Elsevier Ltd. All rights reserved.

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  • Mangromicin C, a new analog of mangromicin.

    Takuji Nakashima, Yoshiyuki Kamiya, Masato Iwatsuki, Noriko Sato, Yōko Takahashi, Satoshi Ōmura

    The Journal of antibiotics   68 ( 3 ) 220 - 2  2015.03  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

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  • Trichopolyn VI: a new peptaibol insecticidal compound discovered using a recombinant Saccharomyces cerevisiae screening system.

    Takuya Suga, Yukihiro Asami, Shohei Hashimoto, Kenichi Nonaka, Masato Iwatsuki, Takuji Nakashima, Yoshihiro Watanabe, Ryohei Sugahara, Takahiro Shiotsuki, Takenori Yamamoto, Yasuo Shinohara, Naoya Ichimaru, Masatoshi Murai, Hideto Miyoshi, Satoshi Ōmura, Kazuro Shiomi

    The Journal of general and applied microbiology   61 ( 3 ) 82 - 7  2015  [Refereed]  [Domestic journal]

     View Summary

    In the course of searching for insecticides from soil microorganisms, we found that a fermentation broth of the fungus, Trichoderma brevicompactum FKI-6324, produced Trichopolyn VI, a new peptaibol, which possessed significant insecticidal potential. Spectroscopic analysis showed the compound to be a new trichopolyn I derivative. This paper describes the isolation, structure elucidation and biological activity of trichopolyn VI.

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  • Cytoprotective effects of grape seed extract on human gingival fibroblasts in relation to its antioxidant potential.

    Yusuke Katsuda, Yoshimi Niwano, Takuji Nakashima, Takayuki Mokudai, Keisuke Nakamura, Satomi Oizumi, Taro Kanno, Hiroyasu Kanetaka, Hiroshi Egusa

    PloS one   10 ( 8 ) e0134704  2015  [Refereed]  [International journal]

     View Summary

    Cytoprotective effects of short-term treatment with grape seed extract (GSE) upon human gingival fibroblasts (hGFs) were evaluated in relation to its antioxidant properties and compared with those of a water-soluble analog of vitamin E: trolox (Tx). GSE and Tx showed comparable antioxidant potential in vitro against di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH; a stable radical), hydroxyl radical (•OH), singlet oxygen (1O2), and hydrogen peroxide (H2O2). Pretreatment or concomitant treatment with GSE for 1 min protected hGFs from oxidative stressors, including H2O2, acid-electrolyzed water (AEW), and 1O2, and attenuated the intracellular formation of reactive oxygen species induced by H2O2 and AEW. Tx also reduced the H2O2- and AEW-induced intracellular formation of reactive oxygen species, but showed no cytoprotective effects on hGFs exposed to H2O2, AEW, or 1O2. These results suggest that the cytoprotective effects of GSE are likely exerted independently of its antioxidant potential.

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  • Acceleration of proliferative response of mouse fibroblasts by short-time pretreatment with polyphenols.

    Makoto Tsuruya, Yoshimi Niwano, Keisuke Nakamura, Taro Kanno, Takuji Nakashima, Hiroshi Egusa, Keiichi Sasaki

    Applied biochemistry and biotechnology   174 ( 6 ) 2223 - 35  2014.11  [Refereed]  [International journal]

     View Summary

    Under the hypothesis that photo-irradiated proanthocyanidin could accelerate wound healing through reactive oxygen species (ROS) formation, we examined the effect of proanthocyanidin on 3T3-L1 mouse fibroblasts with or without photo-irradiation. As a result, irrespective of presence or absence of photo-irradiation, only 1 min exposure of the cells to proanthocyanidin resulted in accelerated proliferation of the cells in a concentration-dependent manner. Similarly to proanthocyanidin, 1 min pretreatment with catechin, caffeic acid, and chlorogenic acid accelerated the proliferative response, but gallic acid, epicatechin gallate, epigallocatechin, and epigallocatechin gallate failed. If incorporated active ingredient such as proanthocyanidin for such a short time as 1 min accelerates the proliferation response, a bioassay was conducted by utilizing antioxidant potential of proanthocyanidin. That is, intracellular oxidation of 2',7'-dichlorodihydrofluorescin induced by H2O2 was significantly inhibited when the cells were pretreated with proanthocyanidin for 1 min, suggesting that incorporated proanthocyanidin into the cells exerted antioxidant effect. This was also supported by a liquid chromatography/mass spectrometry analysis in which incorporation of proanthocyanidin components such as catechin monomers and dimers into the cells within 1 min was confirmed. These results suggest that active polyphenolic compounds such as proanthocyanidin, catechin, caffeic acid, and chlorogenic acid incorporated into the cells in such a short time as 1 min could accelerate the proliferative response of the cells.

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  • Rhizocola hellebori gen. nov., sp. nov., an actinomycete of the family Micromonosporaceae containing 3,4-dihydroxydiaminopimelic acid in the cell-wall peptidoglycan.

    Atsuko Matsumoto, Yoko Kawaguchi, Takuji Nakashima, Masato Iwatsuki, Satoshi Ōmura, Yōko Takahashi

    International journal of systematic and evolutionary microbiology   64 ( Pt 8 ) 2706 - 2711  2014.08  [Refereed]  [International journal]

     View Summary

    An actinomycete strain, K12-0602(T), was isolated from the root of a Helleborus orientalis plant in Japan. The 16S rRNA gene sequence of strain K12-0602(T) showed that it had a close relationship with members of the family Micromonosporaceae and the 16S rRNA gene sequence similarity values between strain K12-0602(T) and type strains of type species of 27 genera belonging to the family Micromonosporaceae were below 96.2%. MK-9 (H4) and MK-9 (H6) were detected as major menaquinones, and galactose, xylose, mannose and ribose were present in the whole-cell hydrolysate. The acyl type of the peptidoglycan was glycolyl. Major fatty acids were iso-C(15 : 0), iso-C(16 : 0), C(17 : 1)ω9c and anteiso-C(17 : 0). Phosphatidylethanolamine was detected as the phospholipid corresponding to phospholipid type II. The G+C content of the genomic DNA was 67 mol%. Analyses of the cell-wall peptidoglycan by TLC and LC/MS showed that it was composed of alanine, glycine, hydroxylglutamic acid and an unknown amino acid, which was subsequently determined to be 3,4-dihydroxydiaminopimelic acid using instrumental analyses, including NMR and mass spectrometry. On the basis of the phylogenetic analysis and chemotaxonomic characteristics, strain K12-0602(T) represents a novel species of a new genus in the family Micromonosporaceae, for which the name Rhizocola hellebori gen. nov., sp. nov. is proposed. The type strain of the type species is K12-0602(T) ( = NBRC 109834(T) = DSM 45988(T)). This is the first report, to our knowledge, of 3,4-dihydroxydiaminopimelic acid being found as a diamino acid in bacterial cell-wall peptidoglycan.

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  • Mangromicins, six new anti-oxidative agents isolated from a culture broth of the actinomycete, Lechevalieria aerocolonigenes K10-0216.

    Takuji Nakashima, Yoshiyuki Kamiya, Masato Iwatsuki, Yōko Takahashi, Satoshi Ōmura

    The Journal of antibiotics   67 ( 7 ) 533 - 9  2014.07  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

     View Summary

    We have been continually searching for novel chemical compounds from culture broths of various actinomycetes using a physicochemical screening system. During the course of this program, we have previously reported the discovery of two new natural products, designated mangromicins A and B, discovered in a broth of a rare actinomycete strain, Lechevalieria aerocolonigenes K10-0216. Mangromicins have a unique and rare structure, a cyclopentadecane skeleton with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. New mangromicin analogs were isolated by using an improved production medium. As a consequence, six analogs, together with mangromicins A and B, were isolated from a cultured broth of L. aerocolonigenes K10-0216. We named them mangromicins D, E, F, G, H and I. All mangromicins showed radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and nitric oxide generated from LPS-stimulated RAW264.7 cells, a murine macrophage cell line. Among the analogs, mangromicins A and I showed the most potent DPPH radical scavenging activity and nitric oxide scavenging activity, respectively.

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  • Mangromicins A and B: structure and antitrypanosomal activity of two new cyclopentadecane compounds from Lechevalieria aerocolonigenes K10-0216.

    Takuji Nakashima, Masato Iwatsuki, Junya Ochiai, Yoshiyuki Kamiya, Kenichiro Nagai, Atsuko Matsumoto, Aki Ishiyama, Kazuhiko Otoguro, Kazuro Shiomi, Yōko Takahashi, Satoshi Ōmura

    The Journal of antibiotics   67 ( 3 ) 253 - 60  2014.03  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Two new cyclopentadecane antibiotics, named mangromicins A and B, were separated out from the culture broth of Lechevalieria aerocolonigenes K10-0216 by Diaion HP-20, silica gel and ODS column chromatography, and were finally purified by HPLC. The chemical structures of the two novel compounds were elucidated by instrumental analyses, including various NMR, MS and X-ray crystallography. Mangromicins A and B consist of cyclopentadecane skeletons with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. Mangromicins A and B showed in vitro antitrypanosomal activity with IC50 values of 2.4 and 43.4 μg ml(-1), respectively. The IC50 values of both compounds were lower than those of cytotoxicity against MRC-5 human fetal lung fibroblast cells.

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    39
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  • Trehangelins A, B and C, novel photo-oxidative hemolysis inhibitors produced by an endophytic actinomycete, Polymorphospora rubra K07-0510.

    Takuji Nakashima, Ryuki Okuyama, Yoshiyuki Kamiya, Atsuko Matsumoto, Masato Iwatsuki, Yuki Inahashi, Kenzaburo Yamaji, Yōko Takahashi, Satoshi Ōmura

    The Journal of antibiotics   66 ( 6 ) 311 - 7  2013.06  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Three new natural products, designated trehangelins A, B and C, were isolated by solvent extraction, silica gel and octadecylsilyl silica gel column chromatographies and subsequent preparative HPLC from the cultured broth of an endophytic actinomycete strain, Polymorphospora rubra K07-0510. The trehangelins consisted of a trehalose moiety and two angelic acid moieties. Trehangelins A (IC50 value, 0.1 mg ml(-1)) and C (IC50 value, 0.4 mg ml(-1)), with symmetric structures, showed potent inhibitory activity against hemolysis of red blood cells induced by light-activated pheophorbide a. However, trehangelin B, with an asymmetric structure, displayed only a slight inhibition (IC50 value, 1.0 mg ml(-1)).

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    32
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  • Generation of superoxide anions by a glycation reaction in conventional laboratory media.

    Takuji Nakashima, Satoshi Omura, Yōko Takahashi

    Journal of bioscience and bioengineering   114 ( 3 ) 275 - 80  2012.09  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

     View Summary

    We reported that generation of superoxide anion (O(2)(-)) was detected from conventional laboratory media. The generated O(2)(-) is non-enzymatic converted to hydroxyl radicals, which cause damage to lipids, proteins, and nucleic acids. However, the O(2)(-) generating mechanism from culture media is unclear. We considered that the O(2)(-) generation was implicated in a glycation reaction between reducing sugar and proteins, which is the early stage of Maillard reaction. It has been suggested that the glycated proteins, such as Schiff base and Amadori compounds, undergo a spontaneous autoxidation reaction, catalyzed by transition metal ions, involving the O(2)(-) generation. Therefore, we investigated the effect of Chelex 100 on the O(2)(-) generation from brain-heart-infusion (BHI) medium, which is a nutritional culture medium for bacteria. However, the O(2)(-) generation from the BHI medium treated with Chelex 100 was significantly increased in comparison to it treated without Chelex 100. The quantity of O(2)(-) generation from BHI medium was significantly increased by addition of glucose, and in alkaline environment as well as a glycation reaction model system that autoclaved a mixture solution of glucose and tryptophan. In addition, the O(2)(-) generation from BHI medium was significantly inhibited by pyridoxamine that is a Maillard reaction inhibitor. Therefore, it was suggested that the O(2)(-) generation from BHI medium is closely related to the glycation reaction of amide compounds such as proteins containing in the medium without the transition metals.

    DOI PubMed

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    10
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  • Transitional reactive oxygen species (ROS) production in fertilized egg embryos of devil stinger (Inimicus japonicus), a marine fish species.

    Daekyung Kim, Sayaka Naruse, Kazushi Kadomura, Takuji Nakashima, Zedong Jiang, Yasuhiro Yamasaki, Kenichi Yamaguchi, Tatsuya Oda

    Bioscience, biotechnology, and biochemistry   76 ( 8 ) 1561 - 4  2012  [Refereed]  [International journal]

     View Summary

    A time-course analysis of reactive oxygen species (ROS) generation in fertilized eggs of the devil stinger (Inimicus japonicus) from 0 h post-fertilization (hpf) to the early larval stage indicated that the ROS level was highest in the 22 hpf embryo, and declined thereafter. Phorbol myristate acetate (PMA) had no effect on ROS generation by the 22 hpf embryo, whereas PMA significantly increased larval ROS generation, suggesting that the ROS generation mechanisms of the 22 hpf embryo and larva are different at least in terms of PMA-responsiveness. Our results suggest the presence of a specific ROS generation system in devil stinger embryo which can be transitionally activated during embryogenesis.

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    1
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  • Characteristics of Anoxybacillus sp. MU3 Isolated from a Hot Spring and Its Application to the Hyper Thermal Solubilization of Sewage Sludge

    Nakamichi, T, Nakashima, T, Fujisaki, H, Takamatsu, N, Muramatsu, T, Takahashi, Y, Ishibashi, Y

    ENVIRONMENTAL ENGINEERING SCIENCE   28 ( 1 ) 86 - 86  2011.01  [Refereed]

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  • In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationships.

    Masato Iwatsuki, Kazuhiko Otoguro, Aki Ishiyama, Miyuki Namatame, Aki Nishihara-Tukashima, Junko Hashida, Takuji Nakashima, Rokuro Masuma, Yoko Takahashi, Haruki Yamada, Satoshi Omura

    The Journal of antibiotics   63 ( 10 ) 619 - 22  2010.10  [Refereed]  [Domestic journal]

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    16
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  • Generation of reactive oxygen species from conventional laboratory media.

    Takuji Nakashima, Tamae Seki, Atsuko Matsumoto, Hiromi Miura, Emiko Sato, Yoshimi Niwano, Masahiro Kohno, Satoshi Omura, Yōko Takahashi

    Journal of bioscience and bioengineering   110 ( 3 ) 304 - 7  2010.09  [Refereed]  [Domestic journal]

    Authorship:Lead author

     View Summary

    We previously reported that superoxide anion was generated from glucose-peptone-meat extract medium. We found that superoxide anion was generated from other conventional laboratory media, Nutrient Broth, Tryptic Soy Broth, and Mueller Hinton Broth as well as glucose-peptone-meat extract medium. The glucose-peptone-meat extract medium consisting of 1% glucose, 0.5% peptone, 0.5% meat extract, and 0.3% NaCl showed the highest superoxide anion generation among the media tested. The meat extract and peptone, which are natural nutrient sources in the medium, showed an increase in absorbance intensity by WST-1 formazan products upon reaction with superoxide anion. The specific type of reactive oxygen species was measured by SOD-inhibitable reduction of cytochrome c and WST-1 (for superoxide anion), Fluoro H(2)O(2) kit (for hydrogen peroxide), hydroxyphenyl fluorescein (for hydroxyl radical), and Singlet Oxygen Sensor Green (for singlet oxygen). The generation of hydroxyl radical was also evaluated by ESR-spin trapping method. We detected superoxide anion, hydrogen peroxide, and hydroxyl radical but not singlet oxygen. These results suggest that the superoxide anion spontaneously generated from glucose-peptone-meat extract medium is finally converted to hydroxyl radical.

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    19
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  • In vitro and in vivo anti-Trypanosoma brucei activities of phenazinomycin and related compounds.

    Kazuhiko Otoguro, Aki Ishiyama, Masato Iwatsuki, Miyuki Namatame, Aki Nishihara-Tukashima, Takuji Nakashima, Seiji Shibahara, Shinichi Kondo, Haruki Yamada, Satoshi Omura

    The Journal of antibiotics   63 ( 9 ) 579 - 81  2010.09  [Refereed]  [Domestic journal]

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    13
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  • Isolation and Characterization of Marine and Terrestrial Actinomycetes Using a Medium Supplemented with NaCl

    Chiaki Imada, Syunpei Masuda, Takeshi Kobayashi, Naoko Hamada-Sato, Takuji Nakashima

    Actinomycetologica   24   12 - 17  2010.06  [Refereed]

    DOI

  • Productivity of Bioactive Compounds in Streptomyces Species Isolated from Nagasaki Marine Environments.

    Takuji Nakashima, Kozue Anzai, Rieko Suzuki, Natsumi Kuwahara, Satoshi Takeshita, Akihiko Kanamoto, Katsuhiko Ando

    Actinomycetologica   23 ( 1 ) 16 - 20  2009.06  [Refereed]

    Authorship:Lead author, Corresponding author

     View Summary

    Based on a Blast search of 16S rRNA sequences of Streptomyces from marine environments of Nagasaki, Japan, 64 isolates showed the highest similarity scores with NBRC strains. Only 5 out of these 64 strains showed exactly the same biological profiles as the approximately 900 strains preserved at NBRC strains, while the remaining isolates showed different biological profiles. This suggests that the genus Streptomyces has the ability to produce a wide variety of unknown bioactive metabolites.

    DOI CiNii

  • Discovery of a pimaricin analog JBIR-13, from Streptomyces bicolor NBRC 12746 as predicted by sequence analysis of type I polyketide synthase gene.

    Hisayuki Komaki, Miho Izumikawa, Jun-ya Ueda, Takuji Nakashima, Shams Tabrez Khan, Motoki Takagi, Kazuo Shin-ya

    Applied microbiology and biotechnology   83 ( 1 ) 127 - 33  2009.05  [Refereed]  [International journal]

     View Summary

    Sequence analysis of ketosynthase domain amplicons from Streptomyces bicolor NBRC 12746(T) revealed the presence of previously unreported type I polyketide synthases (PKS-I) genes. The clustering of these genes with the reference PKS-1 sequences suggested the possibility to produce a polyene compound similar to pimaricin. Thus, the cultured sample from NBRC 12746(T) was analyzed for the production of polyene compounds. The strain produced an antifungal compound which displayed the UV absorption spectrum of tetraene macrolides. The structure determination based on the spectroscopic analysis of the purified compound resulted in the identification of a novel pimaricin analog JBIR-13 (1). This study therefore strongly suggested that a careful analysis of PKS-I genes can provide valuable information in the search of novel bioactive compounds within a class predicted from phylogenetic analysis.

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    14
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  • Physicochemical characters of a tyrosinase inhibitor produced by Streptomyces roseolilacinus NBRC 12815.

    Takuji Nakashima, Kozue Anzai, Natsumi Kuwahara, Hisayuki Komaki, Shinji Miyadoh, Shigeaki Harayama, Ma Diarey Bordon Tianero, Junichi Tanaka, Akihiko Kanamoto, Katsuhiko Ando

    Biological & pharmaceutical bulletin   32 ( 5 ) 832 - 6  2009.05  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

     View Summary

    We examined the biological activities present in Streptomyces strains preserved at the National Institute of Technology and Evaluation Biological Resource Center, and found a metabolite of Streptomyces roseolilacinus NBRC 12815 that showed a potent anti-tyrosinase activity. The compounds with anti-tyrosinase activity were purified by several chromatographic procedures. Final HPLC analysis revealed at least two anti-tyrosinase compounds with different retention times (12815A and B). The identification of two anti-tyrosinase compounds was performed with instrumental analysis and database search. The results obtained suggest that the active compounds are SF 2583A and B. Compound 12815A (IC(50) values; about 9 microM) showed more potent tyrosinase inhibition than compound 12815B (IC(50) values; about 1086 microM). The only structural difference between 12815A and B is the presence of an additional chloric atom. In addition, the activity of 12815A was markedly decreased under acidic conditions, resulting in irreversible inactivation. However, the inactivated 12815A still exhibited residual activity when exposed to detergent, Tween 80. These results suggest that the chlorine and the hydration water are very important in the exertion of anti-tyrosinase activity by 12815A.

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    12
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  • Production of bioactive compounds based on phylogeny in the genus Penicillium preserved at NBRC.

    Takuji Nakashima, Shinzo Mayuzumi, Shigeki Inaba, Ju-Young Park, Kozue Anzai, Rieko Suzuki, Natsumi Kuwahara, Noriko Utsumi, Fumie Yokoyama, Hajime Sato, Izumi Okane, Yasuhisa Tsurumi, Katsuhiko Ando

    Bioscience, biotechnology, and biochemistry   72 ( 11 ) 3051 - 4  2008.11  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Penicillium strains (n=394) preserved at NBRC (the NITE Biological Resource Center) were compared as to groupings (11 species-clusters) based on phylogeny and the production of bioactive compounds. The strains in two clusters, of which P. chrysogenum and P. citrinum are representative, showed higher rates of positive strains with multi-biological activities.

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    4
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  • Effects of antifungal agents on red tide phytoplankton: possibility of a novel preventive tool

    Takuji Nakashima, Yoshimi Niwano, Satoshi Takeshita

    AQUACULTURE RESEARCH   39 ( 12 ) 1346 - 1350  2008.09  [Refereed]

    Authorship:Lead author, Corresponding author

    DOI

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  • Characterization of Burkholderia sp. Y1 Isolated from Oil Polluted Soil

    WATARU MURAOKA, TAKUJI NAKASHIMA, YASUHIRO TABIRA, HIROSHI EGUCHI, KAZUYUKI IMAGAWA, YOSHIMASA MASTUMURA, SATOSHI TAKESHITA, TAKEHIRO TAKEMASA

       2008.08

    Authorship:Last author

  • Taxonomic distribution of Streptomyces species capable of producing bioactive compounds among strains preserved at NITE/NBRC.

    Kozue Anzai, Michiyo Ohno, Takuji Nakashima, Natsumi Kuwahara, Rieko Suzuki, Tomohiko Tamura, Hisayuki Komaki, Shinji Miyadoh, Shigeaki Harayama, Katsuhiko Ando

    Applied microbiology and biotechnology   80 ( 2 ) 287 - 95  2008.08  [Refereed]  [International journal]

    Authorship:Corresponding author

     View Summary

    The taxonomic distribution of Streptomyces species capable of producing bioactive compounds was investigated. Nine hundred and six strains were tested for the following four biological activities: antimicrobial, anti-tyrosinase, antioxidant, and hemolytic. Approximately 30% of strains tested showed antimicrobial activities, except for anti-Escherichia coli activity, which was present in only a few strains, while the rates of positivity for the anti-tyrosinase, antioxidant, and hemolytic activities were much lower. The distribution of Streptomyces strains capable of producing bioactive compounds was analyzed by the taxonomy based on 16S rRNA gene sequences. Moreover, the strains of Streptomyces hygroscopicus tested were divided into two clades in the phylogenetic tree, and all of the strains belonging to one clade showed antibacterial and antifungal activities. For detection of polyenes, the UV-visible spectra of metabolic extracts in the strains showing antifungal activities were measured. It was suggested that Streptomyces strains produce universal active compounds under different growth conditions. Further information on the relationship between the microbial taxonomy and the bioactive compounds produced would be useful for the utilization of industrial microorganisms.

    DOI PubMed

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    10
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  • Comparison of groupings among members of the genus Aspergillus based on phylogeny and production of bioactive compounds.

    Kozue Anzai, Shinzo Mayuzumi, Takuji Nakashima, Hajime Sato, Shigeki Inaba, Ju-Young Park, Natsumi Kuwahara, Rieko Suzuki, Noriko Utsumi, Fumie Yokoyama, Yuko Ohfuku, Katsuhiko Ando

    Bioscience, biotechnology, and biochemistry   72 ( 8 ) 2199 - 202  2008.08  [Refereed]  [International journal]

    Authorship:Corresponding author

     View Summary

    Three hundred sixty-six Aspergillus strains preserved at the National Institute of Technology and Evaluation (NITE) were compared as to phylogenetic relationships (11 species-clusters) based on the DNA sequences of the D1/D2 domains of LSU rRNA and ITS regions, including the 5.8S rRNA and biological activities of their secondary metabolites. The results showed relatively well correlation between the phylogenetic distribution and the production of bioactive compounds, especially, antimicrobial activities.

    DOI PubMed

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    6
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  • Actinomycete bacteria isolated from the sediments at coastal and offshore area of Nagasaki Prefecture, Japan: diversity and biological activity.

    Kozue Anzai, Takuji Nakashima, Natsumi Kuwahara, Rieko Suzuki, Yuko Ohfuku, Satoshi Takeshita, Katsuhiko Ando

    Journal of bioscience and bioengineering   106 ( 2 ) 215 - 7  2008.08  [Refereed]  [Domestic journal]

    Authorship:Corresponding author

     View Summary

    About 800 strains of actinomycetes were isolated from marine environments around Nagasaki Prefecture, Japan. The isolates were compared with taxa and biological activities of their secondary metabolites. It is suggested that a variety of actinomycetes are isolated from different marine environments.

    DOI PubMed

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    11
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  • Cytotoxic action mode of a novel porphyrin derivative isolated from harmful red tide dinoflagellate Heterocapsa circularisquama

    Daekyung Kim, Yousuke Miyazaki, Takuji Nakashima, Takashi Iwashita, Tsuyoshi Fujita, Kenichi Yamaguchi, Kwang-Sik Choi, Tatsuya Oda

    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY   22 ( 3 ) 158 - 165  2008  [Refereed]

     View Summary

    Heterocapsa circularisquama is known to cause lethal effect on bivalves, but toxic effect on fish has not been reported yet. Recently, we have found that H. circularisquama has potent light-dependent hemolytic toxins. Based on the chemical structural analysis, one of the hemolytic toxins named H2-a was found to be a novel porphyrin derivative with similar structure to pyropheophorbide a methyl ester (PME), a well-known photoactive hemolytic agent (Miyazaki et al., Aquatic Toxicol. 2005;73:382-393). To clarify the cytotoxic action mode of H2-a, we examined the effects of 1-12-a on HeLa cells in comparison with PME. The cytotoxicities of both reagents were strictly light dependent, and no significant cytotoxic effects including cellular morphological changes were induced without light illumination. The dose response curves revealed that H2-a showed stronger cytotoxicity to HeLa cells than PME. Fluorescence microscopic observation suggested that 1-12-a tends to accumulate in the plasma membrane, whereas PME seems to distribute entire cytoplasm. Although PME induced typical apoptotic nuclear morphological changes and DNA fragmentation in HeLa cells, no such apoptosis-inducing ability of H2-a was observed. Among the radical scavengers, histidine significantly inhibited the cytotoxic activity of H2-a, suggesting the involvement of singlet oxygen in the cytotoxicity. These results suggest that the cytotoxic mechanism of H2-a is necrotic rather than apoptosis differing from PME, even though these are structurally quite similar to each other. The relatively high affinity of 1-12-a to the plasma membrane might result in the potent and quick cytotoxicity without induction of apoptotic signal transduction. (C) 2008 Wiley Periodicals, Inc.

    DOI PubMed

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    9
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  • A prodigiosin analogue inactivates NADPH oxidase in macrophage cells by inhibiting assembly of p47phox and Rac.

    Takuji Nakashima, Takashi Iwashita, Tsuyoshi Fujita, Emiko Sato, Yoshimi Niwano, Masahiro Kohno, Shunsuke Kuwahara, Nobuyuki Harada, Satoshi Takeshita, Tatsuya Oda

    Journal of biochemistry   143 ( 1 ) 107 - 15  2008.01  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Prodigiosins are natural red pigments that have multi-biological activities. Recently, we discovered a marine bacterial strain, which produces a red pigment. Extensive two-dimensional nuclear magnetic resonance and mass spectrometry analysis showed that the pigment is a prodigiosin analogue (PG-L-1). Here, we investigated the effect of PG-L-1 on NADPH oxidase activity in macrophage cells. PG-L-1 significantly inhibited superoxide anion (O(2)(-)) production by phorbol 12-myristate 13-acetate (PMA)-stimulated RAW 264.7 cells, a mouse macrophage cell line. The ED(50) value was estimated to be approximately 0.3 microM. PG-L-1 had no direct scavenging effect on O(2)(-) generated by hypoxanthine/xanthine oxidase system in electron spin resonance-spin trapping determinations, suggesting that this compound directly acts on the O(2)(-) production system, NADPH oxidase, in macrophage cells. We further investigated the effect of PG-L-1 on the behaviour of the cytosolic components of the NADPH oxidase, p67(phox), p47(phox), p40(phox), Rac and protein kinase C (PKC), in PMA-stimulated RAW 264.7 cells. Although PG-L-1 showed no effect on the activation of PKC, the immunoblotting analysis using specific antibodies showed that PG-L-1 strongly inhibits the association of p47(phox) and Rac in the plasma membrane of PMA-stimulated RAW 264.7 cells. These results suggest that PG-L-1 inactivates NADPH oxidase through the inhibition of the binding of p47(phox) and Rac to the membrane components of NADPH oxidase.

    DOI PubMed

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    15
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  • Ciclopirox olamine directly scavenges hydroxyl radical.

    Emiko Sato, Masahiro Kohno, Takuji Nakashima, Yoshimi Niwano

    International journal of dermatology   47 ( 1 ) 15 - 8  2008.01  [Refereed]  [International journal]

    DOI PubMed

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    8
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  • A novel indole-diterpenoid, JBIR-03 with anti-MRSA activity from Dichotomomyces cejpii var. cejpii NBRC 103559.

    Masahiro Ogata, Jun-ya Ueda, Midori Hoshi, Junko Hashimoto, Takuji Nakashima, Kozue Anzai, Motoki Takagi, Kazuo Shin-ya

    The Journal of antibiotics   60 ( 10 ) 645 - 8  2007.10  [Refereed]  [Domestic journal]

     View Summary

    A new indole-diterpene, JBIR-03 (1), was isolated from the fungus Dichotomomyces cejpii var. cejpii NBRC 103559 and its structure was determined based on the spectroscopic data. 1 exhibited anti-MRSA (methicillin-resistant Staphylococcus aureus) activity and antifungal activity against apple Valsa canker-causing fungus, Valsa ceratosperma, while it exhibited no toxicity towards human cancer cells.

    DOI PubMed

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    41
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  • A novel nuclear export inhibitor JBIR-02, a new piericidin discovered from Streptomyces sp. ML55.

    Jun-Ya Ueda, Takushi Togashi, Susumu Matukura, Aya Nagai, Takuji Nakashima, Hisayuki Komaki, Kozue Anzai, Shigeaki Harayama, Takayuki Doi, Takashi Takahashi, Tohru Natsume, Yasutomo Kisu, Naoki Goshima, Nobuo Nomura, Motoki Takagi, Kazuo Shin-Ya

    The Journal of antibiotics   60 ( 7 ) 459 - 62  2007.07  [Refereed]  [Domestic journal]

     View Summary

    A new member of the piericidin family, JBIR-02, was isolated from mycelium of Streptomyces sp. ML55 together with two known piericidin derivatives, piericidin A(1) and IT-143-B. The structure was determined on the basis of spectroscopic data. JBIR-02 inhibited nuclear export of beta-arrestin in HeLa cells at the concentration of 20 microM.

    DOI PubMed

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    8
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  • New aureothin derivative, alloaureothin, from Streptomyces sp. MM23.

    Jun-ya Ueda, Junko Hashimoto, Aya Nagai, Takuji Nakashima, Hisayuki Komaki, Kozue Anzai, Shigeaki Harayama, Takayuki Doi, Takashi Takahashi, Kazuo Nagasawa, Tohru Natsume, Motoki Takagi, Kazuo Shin-ya

    The Journal of antibiotics   60 ( 5 ) 321 - 4  2007.05  [Refereed]  [Domestic journal]

     View Summary

    A new polypropionate alloaureothin (1) possessing a nitro group, together with a known polypropionate aureothin (2), was isolated from mycelium of Streptomyces sp. MM23. The structure was determined on the basis of spectroscopic data. 1 exhibited growth inhibitory effect against human fibrosarcoma HT1080 cells with an IC50 value of 30 microM.

    DOI PubMed

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    24
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  • Inhibitory or scavenging action of ketoconazole and ciclopiroxolamine against reactive oxygen species released by primed inflammatory cells

    T. Nakashima, E. Sato, Y. Niwano, M. Kohno, W. Muraoka, T. Oda

    British Journal of Dermatology   156 ( 4 ) 720 - 727  2007.04  [Refereed]

    Authorship:Lead author, Corresponding author

     View Summary

    Background: Reactive oxygen species (ROS) released from inflammatory cells constitute one of the critical causative factors in inflammatory skin diseases such as seborrhoeic dermatitis and atopic dermatitis. Objectives: To investigate inhibitory effects of ketoconazole (KCZ) and ciclopiroxolamine (CPO), both of which have been used for the treatment of seborrhoeic dermatitis, on ROS released from inflammatory cells. Methods: The methyl-Cypridina-luciferin analogue-dependent chemiluminescence method was employed for the detection of ROS production by phorbol 12-myristate 13-acetate (PMA)-stimulated inflammatory cells. Moreover, the radical scavenging activities of both agents were examined by using a hypoxanthine-xanthine oxidase system and the stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). NADPH oxidase activity was determined in particulate (membrane) fractions prepared from PMA-stimulated RAW 264·7 cells, a macrophage-like cell line. Results Both of these antifungal agents inhibited PMA-stimulated ROS production. However, only CPO significantly scavenged both ROS generated by the hypoxanthine-xanthine oxidase system and DPPH, and the scavenging activity of CPO seemed to act on ROS other than superoxide anions. Although KCZ inhibited PMA-stimulated ROS production, it did not show radical-scavenging activities. The inhibition of ROS production by KCZ is probably attributable to the inhibition of NADPH oxidase activity. Conclusions: The mechanism of the inhibitory action of KCZ against PMA-stimulated ROS production is distinct from that of CPO. Knowledge of the inhibitory or scavenging effects of both antifungal agents on ROS released from inflammatory cells may be useful in developing a therapeutic strategy for dermatitis. © 2007 The Authors.

    DOI PubMed

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    11
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  • Presence of the distinct systems responsible for superoxide anion and hydrogen peroxide generation in red tide phytoplankton Chattonella marina and Chattonella ovata

    Daekyung Kim, Takuji Nakashima, Yukihiko Matsuyama, Yoshimi Niwano, Kenichi Yamaguchi, Tatsuya Oda

    Journal of Plankton Research   29 ( 3 ) 241 - 247  2007.03  [Refereed]

     View Summary

    Raphidophycean flagellates, Chattonella marina and C. ovata, are harmful red tide phytoplankters
    blooms of these phytoplankters often cause severe damage to fish farming. Previous studies have demonstrated that C. marina and C. ovata continuously produce reactive oxygen species (ROS) such as superoxide anion (O2-) hydrogen peroxide (H2O2) under normal growth conditions, and an ROS-mediated toxic mechanism against fish and other marine organisms has been proposed. Although the exact mechanism of ROS generation in these phytoplankters still remains to be clarified, our previous study suggested that NADPH oxidase-like enzyme located on the cell surface of C. marina may be involved in O2- generation. To investigate the localization of O2- and H 2O2 generation in C. marina and C. ovata, we employed 2-methyl-6(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin-3-one and 5-(and-6)-carboxy-2′,7′-dichlorodihydrodihydrofluorescein dictate, acetyl ester, which are specific fluorescent probe for detecting O 2- and H2O2, respectively. Observation by fluorescence microscopy of live phytoplankters incubated with each probe revealed that O2- is mainly generated on the cell surface, whereas H2O2 is generated in the intracellular compartment in these phytoplankters. When the cells were ruptured by ultrasonic treatment, O2- levels of C. marina and C. ovata decreased significantly, whereas a few times higher levels of H 2O2 were detected in the ruptured cell suspensions when compared with the levels of the live cell suspension. In immunoblotting analysis, the protein recognized by anti-human gp91 phox was detected in both species. These results suggest that, in both phytoplankters, the underlying mechanisms of O2- and H2O2 generation may be distinct and such systems are independently operating in the cells. © The Author 2007. Published by Oxford University Press. All rights reserved.

    DOI

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    46
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  • A selective separation method for slower-growing bacteria from marine soils

    Takuji Nakashima, Wataru Muraoka, Satoshi Takeshita

    INSTRUMENTATION SCIENCE & TECHNOLOGY   35 ( 2 ) 211 - 217  2007.03  [Refereed]

    Authorship:Lead author, Corresponding author

     View Summary

    Egg lecithin greatly reduced the antibacterial activities of chlorhexidine gluconate (CHG). By using this antagonistic action, slower-growing bacteria, for which a longer incubation time was needed for its growth, were isolated from marine soils. The growth of relatively faster-growing bacteria, which formed visible colonies during a 3 day incubating period, was significantly inhibited by treatment with 8 mu g of CHG per mL for 10 min, whereas the addition of egg lecithin to a final concentration of 2%, after the treatment, had no significant effect on the viability of slower-growing bacteria.

    DOI

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  • Some dinophycean red tide plankton species generate a superoxide scavenging substance.

    Emiko Sato, Yoshimi Niwano, Yukihiko Matsuyama, Daekyung Kim, Takuji Nakashima, Tatsuya Oda, Masahiro Kohno

    Bioscience, biotechnology, and biochemistry   71 ( 3 ) 704 - 10  2007.03  [Refereed]  [International journal]

     View Summary

    Recent studies indicate that some raphidophycean red tide flagellates produce substances able to scavenge superoxide, whereas there have been no reports on superoxide scavenger production by dinophycean red tide flagellates. In this study, we examined the superoxide-scavenging activity of aqueous extracts from dinophycean red tide flagellates, Gymnodinium spp., Scrippsiella trochoidea, and Karenia sp., by a luminol analog L-012-dependent chemiluminescence (CL) method and an electron spin resonance (ESR)-spin trapping method, and compared the activity to that of raphidophycean red tide flagellates, Chattonella spp., Heterosigma akashiwo, and Fibrocapsa japonica. In the experiment applying the L-012-dependent CL method, only the aqueous extracts from raphidophycean red tide flagellates showed superoxide-scavenging activity. On the other hand, applying the ESR-spin trapping method, we found that the aqueous extracts from dinophycean red tide flagellates also showed superoxide-scavenging activity. This is the first report on the production of a superoxide-scavenger by dinophycean red tide flagellates.

    DOI PubMed

    Scopus

    12
    Citation
    (Scopus)
  • Mode of action of an antialgal agent produced by a marine gammaproteobacterium against Chattonella marina

    Takuji Nakashima, Daekyung Kim, Yousuke Miyazaki, Kenichi Yamaguchi, Satoshi Takeshita, Tatsuya Oda

    AQUATIC MICROBIAL ECOLOGY   45 ( 3 ) 255 - 262  2006.12  [Refereed]

    Authorship:Lead author, Corresponding author

     View Summary

    A marine gammaproteobacterium, strain MS-02-063, was able to kill Chattonella marina, a noxious red tide phytoplankton. However, the algicidal activity of bacterial cells washed with the planktonic medium was significantly reduced. These results suggest that strain MS-02-063 produces an extracellular substance, the pigment, PG-L-1, that showed a potent algicidal effect on C. marina. The LD50 value of PG-L-1 was calculated to be approximately 8.5 mu g ml(-1). At the approximate LD50 concentration of 10 mu g ml(-1), a morphological change, which seemed to be due to the inhibition of cell division, was observed in C. marina. Almost all cells of C. marina were destroyed readily at 100 mu g ml(-1) of PG-L-1, and the cytostatic activity of PG-L-1 against this phytoplankton was observed at a concentration of 1 mu g ml(-1) during the 5 d of incubation. A sublethal concentration of PG-L-1 of 10 mu g ml(-1) significantly inhibited the reactive oxygen species (ROS) production by C. marina. ROS production has been previously reported to be essential for normal growth of C. marina (Oda et al. 1995; Biosci Biotechnol Biochem 59:2044-2048). Therefore, the inhibitory effect of PG-L-1 on ROS production may lead to growth inhibition of C. marina, at least in part. The pigment, PG-L-1, may be a useful compound not only as an applicable agent for the mitigation of harmful algal blooms, but also as an experimental tool to analyse the ROS production system in a red tide phytoplankton such as C. marina.

    DOI

    Scopus

    16
    Citation
    (Scopus)
  • Producing mechanism of an algicidal compound against red tide phytoplankton in a marine bacterium gamma-proteobacterium.

    Takuji Nakashima, Yousuke Miyazaki, Yukihiko Matsuyama, Wataru Muraoka, Kenichi Yamaguchi, Tatsuya Oda

    Applied microbiology and biotechnology   73 ( 3 ) 684 - 90  2006.12  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Strain MS-02-063, gamma-proteobacterium, isolated from a coast area of Nagasaki, Japan, produced a red pigment which belongs to prodigiosin members. This pigment, PG-L-1, showed potent algicidal activity against various red tide phytoplanktons in a concentration-dependent manner. An understanding of a mechanism of PG-L-1 production by this marine bacterium may yield important new insights and strategies for preventing blooms of harmful flagellate algae in natural marine environments. Therefore, we analyzed the mechanisms of PG-L-1 production. In our previous study, the pigment production by this marine bacterium was completely inhibited at 1.56 microg/ml of erythromycin or 3.13 microg/ml of chloramphenicol, while minimal inhibitory concentrations for cell growth of erythromycin and chloramphenicol against this bacterium were >100 and 25 microg/ml, respectively. It is interesting to note that the ability of the pigment production in erythromycin-treated bacterium recovered by an addition of homoserine lactone. In fact, the pigment production was inhibited by beta-cyclodextrin that inhibits autoinducer activities by a complex with N-acyl homoserine lactones. N-acyl homoserine lactones with autoinducer activities are ubiquitous bacterial signaling molecules that regulate gene expression in a cell density dependent process known as quorum sensing. Therefore, it was suggested that PG-L-1 produced by strain MS-02-063 is controlled by the homoserine lactone quorum sensing. It is speculated that this quorum sensing is involved in the production of algicidal agents of other marine bacteria. This bacterium and other algicidal bacteria might be concerned in regulating the blooms of harmful flagellate algae through the quorum sensing system.

    DOI PubMed

    Scopus

    95
    Citation
    (Scopus)
  • Production of reactive oxygen species (ROS) by devil stinger (Inimicus japonicus) during embryogenesis.

    Kazushi Kadomura, Takuji Nakashima, Maki Kurachi, Kenichi Yamaguchi, Tatsuya Oda

    Fish & shellfish immunology   21 ( 2 ) 209 - 14  2006.08  [Refereed]  [International journal]

     View Summary

    In aqua-cultural industry, the seed production of devil stinger, a valuable fish in Japan, has not succeeded yet due to the cryptogenic mass mortality. We found that survival rate of the larvae of devil stinger increased by the addition of green tea extract rich in catechin into rearing tank. Generation of reactive oxygen species (ROS) was detected in the embryo of devil stinger by chemiluminescence analysis under the normal growth conditions without addition of specific stimulants. Even in the unfertilized egg, certain level of ROS was detected. ROS were continuously detected during the development from fertilized egg to larva and tended to increase gradually. Observation of embryos and post-hatching larvae with hypersensitive photon-counting microscopy indicated that ROS were produced on the surface of embryo and the head region of larva especially peripheries of eyes. When the embryo proteins were analyzed by immunoblotting using antibody against the human neutrophil cytochrome b558 large subunit (gp91 phox), a main band of approximately 91 kDa was detected, suggesting the presence of NADPH oxidase-like ROS generating system in the embryo of devil stinger. After treatment with streptomycin and penicillin G for 1 day, the level of ROS production in larvae decreased with increase in the survival rate of larvae. Our results suggest that devil stinger has ROS generation system that is already activated at fairly early stage of development before the maturation of usual immune system.

    DOI PubMed

    Scopus

    22
    Citation
    (Scopus)
  • Apoptosis-mediated cytotoxicity of prodigiosin-like red pigment produced by gamma-Proteobacterium and its multiple bioactivities.

    Takuji Nakashima, Tadashi Tamura, Maki Kurachi, Kenichi Yamaguchi, Tatsuya Oda

    Biological & pharmaceutical bulletin   28 ( 12 ) 2289 - 95  2005.12  [Refereed]  [Domestic journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Recently we discovered a bacterial strain (MS-02-063) that produces large amounts of red pigment (PG-L-1). Among the cell lines tested, U937 cells showed the highest susceptibility to PG-L-1 toxicity. PG-L-1 induced typical apoptotic nuclear morphological changes, and single cell gel electrophoresis revealed that PG-L-1 caused DNA fragmentation in U937 cells. In PG-L-1 treated U937 cells, the acidic compartment such as lysosomes disappeared, suggesting that PG-L-1-induced disorder of intracellular pH compartmentalization might trigger apoptotic signal. Since p38 MAP kinase inhibitor specifically prevented the PG-L-1 mediated cell death, p38 MAP kinase may be involved in the cytotoxic mechanism. In fact, immunoblot analysis of p38 MAP kinase revealed that phosphorylation of p38 MAP kinase occurred in PG-L-1-treated U937 cells. In addition to the activity to induce apoptotic cell death as reported in several PG family members, our chemiluminescence analysis suggested that PG-L-1 inhibited superoxide generation by 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated U937 cells in a dose-dependent manner. Since PG-L-1 had no effect on the chemiluminescence response caused by xanthine oxidase/hypoxanthine system, PG-L-1 acts on the enzyme system responsible for O(2)(-) generation rather than direct scavenging toward O(2)(-). Our results suggest that PG-L-1 causes multiple biochemical effects on the target cells such as increase in pH in acidic intracellular compartment, activation of p38 MAP kinase, inhibition of O(2)(-) generation, and eventually induces apoptotic cell death.

    PubMed

  • Structure-activity relationship of alginate oligosaccharides in the induction of cytokine production from RAW264.7 cells.

    Mami Iwamoto, Maki Kurachi, Takuji Nakashima, Daekyung Kim, Kenichi Yamaguchi, Tatsuya Oda, Yoshiko Iwamoto, Tsuyoshi Muramatsu

    FEBS letters   579 ( 20 ) 4423 - 9  2005.08  [Refereed]  [International journal]

     View Summary

    Guluronate and mannuronate oligomers with various degree of polymerization were prepared from polyguluronate (PG) and polymannuronate (PM) with an alginate lyase from a Pseudoalteromonas sp., and their activities to induce cytokine secretion from mouse macrophage cell line RAW264.7 cells were examined. Enzymatically depolymerized unsaturated alginate oligomers induced tumor necrosis factor (TNF)-alpha secretion from RAW264.7 cells in a structure-depending manner, while the activities of saturated alginate oligomers prepared by acid hydrolysis were fairly low or only trace levels. These results suggest that unsaturated end-structure of alginate oligomers was important for the TNF-alpha-inducing activity. Among the unsaturated guluronate (G3-G9) and mannuronate (M3-M9) oligomers, G8 and M7 showed the most potent activity, respectively. Bio-Plex assay revealed that interleukin (IL)-1alpha, IL-1beta, and IL-6 secretion from RAW264.7 cells were also induced by unsaturated alginate oligomers with similar structure-activity relationship profiles as seen in TNF-alpha, and the most potent activities were observed with G8 and M7. These results suggest that G8 and M7 may have the most suitable molecular size or entire structural conformation as stimulant for cytokine secretion. Since antibodies to Toll-like receptor (TLR)2 and TLR4 effectively inhibited the G8- and M7-induced production of TNF-alpha, these alginate oligomers may stimulate innate immunity through the pattern recognition receptors on macrophages similar to microbial products.

    PubMed

  • Comparison of the activities of various alginates to induce TNF-alpha secretion in RAW264.7 cells.

    Maki Kurachi, Takuji Nakashima, Chihiro Miyajima, Yoshiko Iwamoto, Tsuyoshi Muramatsu, Kenichi Yamaguchi, Tatsuya Oda

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   11 ( 4 ) 199 - 203  2005.08  [Refereed]  [International journal]

     View Summary

    We compared the abilities of alginate polymers having different molecular sizes and compositions to induce the secretion of tumor necrosis factor (TNF)-alpha in RAW264.7 cells. The molecular sizes and alpha-L-guluronate/beta-D-mannuronate (M/G) ratios of highly purified alginate polymers used in this study were 9000-38 000 and 1.50-3.17, respectively. Among the alginates tested, I-S, which had the highest molecular weight, showed the most potent TNF-alpha-inducing activity. The M/G ratio also seemed to influence this activity, and, among alginates with similar molecular sizes, alginates with a higher M/G ratio tended to show higher activity. Interestingly, the enzymatic depolymerization of I-S with bacterial alginate lyase resulted in a dramatic increase in the TNF-alpha-inducing activity. Such an effect of enzymatic digestion was also observed in a relatively low-molecular-weight alginate (ULV-3), which originally had very low TNF-alpha-inducing activity. Furthermore, the inhibition profiles of the TNF-alpha-inducing activity of enzymatically digested I-S shown by three specific mitogen-activated protein (MAP) kinase inhibitors differed from those of intact I-S. These results suggest that the underlying mechanism of the TNF-alpha-inducing activity of enzymatically depolymerized alginate oligomers is not necessarily the same as that of original alginate polymer.

    PubMed

  • Purification and characterization of photosensitizing hemolytic toxin from harmful red tide phytoplankton, Heterocapsa circularisquama.

    Yousuke Miyazaki, Takuji Nakashima, Takashi Iwashita, Tsuyoshi Fujita, Kenichi Yamaguchi, Tatsuya Oda

    Aquatic toxicology (Amsterdam, Netherlands)   73 ( 4 ) 382 - 93  2005.07  [Refereed]  [International journal]

     View Summary

    We have previously found that the methanol extract prepared from Heterocapsa circularisquama, a harmful red rid dinoflagellate, showed light-dependent hemolytic activity toward rabbit erythrocytes. Interestingly, the cytotoxicity of the extract against HeLa cells was also strictly light-dependent, and no significant toxic effect was observed even at very high concentration in the dark. In this study, the hemolytic agents present in the extract were purified by several chromatographic procedures. Final HPLC analysis revealed that there are at least two hemolytic toxins with different retention times (H2-a and H3-a), which have similar absorption spectra. Although H3-a fraction was contaminated by a trace amount of H2-a, H2-a fraction gave a single peak on a three-dimensional chromatogram. The results of fast atom bombardment (FAB)-mass spectrometry (MS) and electrospray ionization quadrupole time-of-flight (ESI Q-TOF) mass spectrometry analyses suggested that the molecular weight of H2-a was 566. Since nuclear magnetic resonance analysis indicated the presence of a pyrrole ring in H2-a molecule, H2-a may be a porphyrin derivative with similar structure of pyropheophorbide a methyl ester, a well-known photosensitizing hemolytic compound. However, some structural and physicochemical differences were observed between H2-a and pyropheophorbide a methyl ester. Since H2-a showed potent photosensitizing cytotoxicity toward HeLa cells in a concentration-dependent manner as well as hemolytic activity, H2-a may be a novel porphyrin derivative with photosensitizing hemolytic cytotoxicity.

    PubMed

  • Isolation and characterization of light-dependent hemolytic cytotoxin from harmful red tide phytoplankton Chattonella marina.

    Aiko Kuroda, Takuji Nakashima, Kenichi Yamaguchi, Tatsuya Oda

    Comparative biochemistry and physiology. Toxicology & pharmacology : CBP   141 ( 3 ) 297 - 305  2005.07  [Refereed]  [International journal]

     View Summary

    Chattonella marina (C. marina), a raphidophycean flagellate, is a causative organism of red tide, and highly toxic to fish. In this study, we found that the cell-free methanol extract prepared from this flagellate exhibited potent hemolytic activity against rabbit erythrocytes. Interestingly, the hemolytic activity of the extract was absolutely light-dependent, and no hemolytic activity was detected in the dark even at very high concentration. Gel filtration chromatography of the methanol extract on a column of Sephadex LH-20 revealed that the extract contained hemagglutinin as well as hemolytic agents, and the substances responsible for these activities were separately eluted. These results suggest that the hemagglutinating and hemolytic activities were derived from distinct compounds. The hemolytic fraction obtained after gel filtration (F4) caused marked inhibition of the growth of C. marina itself and other species of phytoplanktons. Furthermore, F4 showed a potent cytotoxicity toward various mammalian cultured cell lines including human tumor cells (HeLa cells) in a dose-dependent manner. The cytotoxicity was also light-dependent, and no cytotoxic effect was exhibited in any cell lines tested in the dark. After further purification procedures via preparative thin-layer chromatography and subsequent HPLC, a major hemolytic agent was obtained as highly purified form. Since the methanol extracts prepared from other raphidophycean flagellates such as Heterosigma akashiwo, Olisthodiscus luteus, and Fibrocapsa japonica showed light-dependent hemolytic activity toward rabbit erythrocytes, it was suggested that the light-dependent hemolytic agents commonly exist at least in these raphidophycean flagellates.

    PubMed

  • Evaluation of the anti-Trichophyton activity of a prodigiosin analogue produced by gamma-proteobacterium, using stratum corneum epidermis of the Yucatan micropig.

    Takuji Nakashima, Yoko Kato, Kenichi Yamaguchi, Tatsuya Oda

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   11 ( 3 ) 123 - 8  2005.06  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Prodigiosins (PGs) are known to be a family of natural red pigments, characterized by a common pyrrolydipyrrolylmethane skeleton structure with a C-4 methoxy group, and some of these pigments have been isolated from some microorganisms. Members of the PG family have been reported to show several biological activities, such as immunosuppressive and cytotoxic activities. Recently, we discovered a bacterial strain (MS-02-063), from our microbial library, that produces large amounts of a PG analogue (PG-L-1). In this study, we examined the anti-Trichophyton activity of PG-L-1 (produced by strain MS-02-063) against clinically isolated Trichophyton spp., by a method using stratum corneum epidermis (SCE) of the Yucatan micropig, which is suitable for estimating the antifungal activity of drugs in vitro. In the National Committee for Clinical Laboratory Standards (NCCLS) method, PG-L-1 showed potent antifungal activity against nine clinically isolated strains of Trichophyton spp., although the minimum inhibitory concentration (MIC) values were slightly higher than those of bifonazole. In spite of the lower efficiency of PG-L-1 transfer into SCE from medium than that of bifonazole, PG-L-1 transferred into SCE showed more potent antifungal activity than bifonazole, at lower concentrations.

    PubMed

  • Characterization of bacterium isolated from the sediment at coastal area of Omura Bay in Japan and several biological activities of pigment produced by this isolate.

    Takuji Nakashima, Maki Kurachi, Yoko Kato, Kenichi Yamaguchi, Tatsuya Oda

    Microbiology and immunology   49 ( 5 ) 407 - 15  2005  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Recently we discovered a bacterial strain (MS-02-063) that produces large amounts of red pigment from coastal area of Nagasaki Prefecture, Japan. Comparative 16S rDNA gene sequencing analysis revealed that strain MS-02-063 was phylogenetically closely related to gamma-proteobacterium Hahella sp. MBIC 3957 that produces prodigiosin. However, some physiological and biochemical differences between strain MS-02-063 and Hahella sp. MBIC 3957 were observed. The red pigment (RP-063) produced by this isolate was highly purified from the culture supernatant. It was speculated that RP-063 might be prodigiosin-like pigment in physical properties and biological activities such as antibacterial and cytotoxic activity. Antibacterial activity of RP-063 was examined by an agar dilution method. The results indicated that RP-063 showed antibacterial activity for specific for pathogenic gram-positive bacteria such as Staphylococcus aureus. The potency of antibacterial activity against S. aureus was nearly equal to those of tetracycline. Moreover, RP-063 showed inhibition of the superoxide generation by 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mouse macrophage RAW 264.7 cell line. Prodigiosin members have a wide variety of biological properties, including anticancer and antimalarial, etc. Especially, potent immunosuppressive properties have been reported for prodigiosin members with the mechanism of action different from that of the other well known immunosuppressors in atopic dermatitis therapy such as cyclosporin A, FK506 and rapamycin. It is suggested that RP-063 may be able to arrest the inflammation caused by superantigens secreted from S. aureus, which colonized skin on atopic dermatitis as well as suppression of activated lymphocyte proliferation and superoxide generation from leucocytes.

    PubMed

  • Cytotoxicity of a GalNAc-specific C-type lectin CEL-I toward various cell lines.

    Takuya Kuramoto, Hitomi Uzuyama, Tomomitsu Hatakeyama, Tadashi Tamura, Takuji Nakashima, Kenichi Yamaguchi, Tatsuya Oda

    Journal of biochemistry   137 ( 1 ) 41 - 50  2005.01  [Refereed]  [International journal]

     View Summary

    We found that CEL-I was a potent cytotoxic lectin. MDCK, HeLa, and XC cells were highly sensitive to CEL-I cytotoxicity and killed in a dose-dependent manner, whereas CHO, L929, and RAW264.7 cells were relatively resistant to CEL-I, and no significant toxicity was observed up to 10 microg/ml. Among these cell lines, MDCK cells showed the highest susceptibility to CEL-I cytotoxicity. A binding study using FITC-labeled CEL-I (F-CEL-I) revealed that the amounts of bound F-CEL-I on the sensitive cell lines were evidently greater than those on the resistant cell lines, suggesting that the different susceptibility of the cell lines to CEL-I cytotoxicity is partly explained by different efficiencies of binding of CEL-I to these cell lines. Interestingly, the cytotoxicity of CEL-I toward MDCK cells was more potent than those of other lectins such as WGA, PHA-L, and Con A, even though these lectins were capable of binding to MDCK cells at comparable levels to CEL-I. Since the cytotoxicity of CEL-I was strongly inhibited by GalNAc, the binding to cell surface specific carbohydrates is essential for the CEL-I cytotoxicity. The trypan blue dye exclusion test indicated that CEL-I caused a disorder of plasma membrane integrity as a relatively early event. CEL-I failed to induce the release of carboxyfluorescein (CF) from CF-loaded MDCK cells as seen for pore-forming hemolytic isolectin CEL-III, suggesting that the primary cellular target of CEL-I may be the plasma membrane, but its action mechanism differs from that of CEL-III. Although CEL-I induced dramatic cellular morphological changes in MDCK cells, neither typical apoptotic nuclear morphological changes nor DNA fragmentation was observed in CEL-I-treated MDCK cells even after such cellular changes. Our results demonstrated that CEL-I showed a potent cytotoxic effect, especially on MDCK cells, by causing plasma membrane disorder without induction of apoptosis.

    PubMed

  • Experimental tinea unguium model to assess topical antifungal agents using the infected human nail with dermatophyte in vitro.

    Takuji Nakashima, Akira Nozawa, Takao Ito, Toshiro Majima

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   8 ( 4 ) 331 - 5  2002.12  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Therapy for onychomycosis is difficult because a complete cure requires long-term treatment. Although strong systemic antifungal drugs are potent enough to achieve a cure, they often have side effects. Therefore, one approach is to develop a new topical antifungal drug to act directly on the nail tissue. In this study, we developed a new in vitro model for assessing antifungal activity using the human nail. An O-ring was fixed with silicon bond to the dorsal surface of the nail. An antifungal agent applied to the surface will penetrate the nail tissue. The ventral side of the nail was placed on an agar plate inoculated with conidia of Trichophyton mentagrophytes. Nail specimens were infected with the fungi from the agar, and a clear fungal colony formed on the agar surrounding the nail on the fifth day of cultivation. After 14 days, the fungal colony in the control groups was shown to be expanding over the entire nail. The fungal colony in the group treated with sodium pyrithione had disappeared. Although the in vitro antifungal activity of sodium pyrithione has poor potency among the agents used, it showed remarkable antifungal activity, as assessed by image analysis. This model enables one to evaluate the activity of a topical antifungal agent that has penetrated human nail tissue, and it may facilitate research on a topical agent for onychomycosis.

    PubMed

  • Development of a new medium useful for the recovery of dermatophytes from clinical specimens by minimizing the carryover effect of antifungal agents.

    Takuji Nakashima, Akira Nozawa, Takao Ito, Toshiro Majima, Hideyo Yamaguchi

    Microbiology and immunology   46 ( 2 ) 83 - 8  2002  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Two surface-active compounds, egg lecithin and polysorbate 80, usually used as the deactivators of various preservatives were tested whether they also counteract either or all of the three major topical antifungal drugs, bifonazole (BFZ), lanoconazole (LCZ) and terbinafine (TBF). Both egg lecithin and polysorbate 80, when added to culture media up to final concentrations of 1.0 and 0.7%, respectively, antagonized the anti-dermatophytic activity of the three drugs in a concentration-dependent manner. A greater extent of antagonistic action was exerted when the two deactivators combined at their maximal levels tested were added; MIC's of BFZ were increased more than 30-fold and those of LCZ and TBF more than 200-fold compared with the values obtained in the absence of the deactivators. Using the agar medium supplemented with the combined deactivators, culture studies were carried out with skin tissues specimens taken from guinea pigs whose feet were infected with dermatophytes and subsequently treated with 1% topical preparations of the three antifungal drugs. The experimental data from this animal study demonstrated that the combined deactivators-supplemented medium yielded increased numbers of fungi compared with the basal medium. It looks, therefore, likely that the fungal recovery on the former medium more correctly reflects to actual fungal burden in the infected lesions than the latter. All these results suggest that the combined deactivators-supplemented medium is more useful for mycological evaluation of therapeutic efficacy of imidazole and allylamine drugs against dermatophytoses in both preclinical and clinical studies.

    PubMed

  • A novel method using micropig stratum corneum in vitro for the evaluation of anti-Trichophyton mentagrophytes activity.

    Takuji Nakashima, Akira Nozawa, Toshiro Majima

    Microbiology and immunology   46 ( 8 ) 521 - 5  2002  [Refereed]  [International journal]

    Authorship:Lead author, Corresponding author

     View Summary

    Antifungal susceptibility testing under conditions close to clinical status is expected to provide more helpful information than that obtained by a conventional microdilution method. For this purpose, we developed a novel method to evaluate anti-Trichophyton mentagrophytes activity of antifungal agents in vitro by using disks of micropig stratum corneum epidermis (SCE). Basal agar medium containing K2HPO4, MgSO4, CaCl2 and three kinds of antibiotics. Bifonazole (BFZ), lanoconazole (LCZ) or terbinafine (TBF) was added to the basal agar medium to give serially doubling dilutions ranging from 0.0006 to 10 microg/ml. Five-hundred-microl portions of the agar media thus prepared were solidified in wells of flat-bottomed plates. SCE disks (6 mm in diameter) were placed on surfaces of the agar medium and 10(4) conidia of T. mentagrophytes were inoculated on each SCE disk. There was very good correlation between the initial concentration of the antifungal agents added to the basal agar medium (microg/ml) and the concentration of the agents impregnated into the SCE disks (microg/g) (r2>0.99). The minimum inhibitory concentration (MIC) values of BFZ, LCZ and TBF were respectively 26-, 10- and 78-times higher than those measured by the standard microdilution method. From the correlation between the concentration of the agents in the basal medium and that in the SCE disks, the above MIC values corresponded to the concentrations in SCE disks (microg/g), 832.95 for BFZ, 1.42 for LCZ and 8.87 for TBF. This novel method of antidermatophytic susceptibility testing using SCE would be useful as an in vitro screening of proper antimycotics for topical treatment of dermatophytosis.

    PubMed

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    三浦 悠花, 松尾 洋孝, 中島 琢自, 片岡 孝夫, 大西 素子, 木村 賢一

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    日本薬学会年会要旨集(CD-ROM)   140年会   27P - pm160  2020.03

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    日本化学会春季年会講演予稿集(CD-ROM)   100th  2020

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    J-GLOBAL

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    日本放線菌学会大会講演要旨集   34回   92 - 92  2019.09

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    中島 琢自, 松尾 洋孝, 高橋 洋子, 大村 智

    日本生物工学会大会講演要旨集   2019年   85 - 85  2019.08

  • 顕微ラマン分光法及び多変量スペクトル分解法を用いた生理活性物質penicillin及びavermectinの菌体内検出

    堀井 俊平, 安藤 正浩, 中島 琢自, アショク・サムエル, 松本 厚子, 高橋 洋子, 竹山 春子

    日本生物工学会大会講演要旨集   2019年   212 - 212  2019.08

    J-GLOBAL

  • Treatment of bio-diesel fuel wastewater using aerobic thermophilic bacteria Bacillus licheniformis strain MU11

    Yamano Koji, Watanabe Reito, Kai Hotaka, Yamaguchi Masahiro, Nakashima Takuji, Araki Kento, Yakushiji Yuka, Arizono Koji, Ishibashi Yasuhiro

    Journal of Environment and Safety   10 ( 3 ) 177 - 187  2019

     View Summary

    <p>During the production of biodiesel fuel, wastewater containing about 10 to 20% of raw material oil such as glycerin,methanol, soap components and impurities such as unconverted fatty acids is generated. This wastewater can be treated by biological treatment such as activated sludge method, but there is no efficient treatment method. Therefore, in this study, we examined the optimum treatment conditions for the purpose of treating biodiesel fuel wastewater.</p><p>The biodiesel fuel wastewater contains water soluble components and oil and, is emulsified. It was confirmed that the addition of an acid was effective for the decomposition of this emulsion (emulsion break). And that the oil component was separated by the decomposition of the emulsion, then the COD of the aqueous layer could be reduced. Also,substances that are the main cause of organic pollution of biodiesel fuel wastewater after emulsion break are glycerin and methanol. Furthermore, it was shown that in the hybrid condition in which activated sludge and MU11 strain were mixed,the rate of decrease of CODMn was fast compared to other conditions. Finally, Hybrid conditions have been shown to be effective for the treatment of biodiesel fuel wastewater.</p>

    DOI CiNii

  • Physicochemical screeningによる微生物新規物質の探索

    中島琢自

    日本農芸化学会大会講演要旨集(Web)   2019  2019

    J-GLOBAL

  • カルボサイクリックポリケチド化合物の大員環形成メカニズムの解析

    大方葉月, 行吉裕治, 稲橋佑起, 稲橋佑起, 高橋洋子, 大村智, 葛山智久, 中島琢自, 荒川賢治

    日本農芸化学会大会講演要旨集(Web)   2019  2019

    J-GLOBAL

  • Streptomyces griseusにおけるイミニマイシン類の生合成遺伝子群の機能解析

    堤隼馬, 勝山陽平, 手塚武揚, 勝山陽平, 手塚武揚, 宮野怜, 稲橋佑起, 高橋洋子, 中島琢自, 大西康夫

    日本農芸化学会大会講演要旨集(Web)   2019  2019

    J-GLOBAL

  • 顕微ラマン多変量スペクトル分解法を用いた生理活性物質penicillin及びavermectinの菌体内検出

    堀井俊平, 安藤正浩, 安武晃, SAMUEL Ashok, 中島琢自, 松本厚子, 高橋洋子, 竹山春子

    日本化学会春季年会講演予稿集(CD-ROM)   99th  2019

    J-GLOBAL

  • 深海由来糸状菌Penicillium sp.FKJ-0123株が生産する新規シンナモイルトリペプチドについて

    松尾洋孝, 目代貴之, 野中健一, 長野由梨子, 矢吹彬憲, 藤倉克則, 庭野吉己, 高橋洋子, 大村智, 中島琢自

    日本農芸化学会大会講演要旨集(Web)   2019  2019

    J-GLOBAL

  • Physicochemical screeningによる新規化合物の探索-Trichoderma virens FKI-7573株が生産する新規含窒素化合物について-

    宮野怜, 松尾洋孝, 野中健一, 目代貴之, 庭野吉己, 塩見和朗, 高橋洋子, 大村智, 中島琢自

    日本農芸化学会大会講演要旨集(Web)   2019  2019

    J-GLOBAL

  • Treatment of bio-diesel fuel wastewater using aerobic thermophilic bacteria Bacillus licheniformis strain MU11

    山野浩二, 渡邉励人, 甲斐穂高, 山口雅裕, 中島琢自, 荒木賢人, 藥師寺佑佳, 有薗幸司, 石橋康弘

    環境と安全(Web)   10 ( 3 )  2019

    J-GLOBAL

  • エルゴステロール修飾シリカゲルの特徴と新規化合物の探索

    伊豆田祥子, 宮野怜, 松本厚子, 松本厚子, 高橋洋子, 大村智, 中島琢自

    日本放線菌学会大会講演要旨集   34th  2019

    J-GLOBAL

  • Streptomyces sp.KO-7888のSARP family regulator発現株が生産する新規物質Sarpeptinについて

    稲橋佑起, KOOMSIRI Wilaiwan, LEETANASAKSAKUL Kantinan, 塩見和朗, 高橋洋子, 大村智, SAMBORSKYY Markiyan, LEADLAY Peter F., WATTANA-AMORN Pakorn, THAMCHAIPENET Arinthip, 中島琢自

    日本放線菌学会大会講演要旨集   34th  2019

    J-GLOBAL

  • 顕微ラマン多変量スペクトル分解法を用いた放線菌S.avermitilisにおける生理活性物質avermectinの菌体内検出

    堀井俊平, 中島琢自, 武晃, 安藤正浩, 松本厚子, 高橋洋子, 竹山春子

    日本放線菌学会大会講演要旨集   34th  2019

    J-GLOBAL

  • 微生物ダークマターが創り出す未知物質の探索

    中島琢自, 松尾洋孝, 高橋洋子, 大村智

    日本生物工学会大会講演要旨集   71st   85 - 85  2019

    J-GLOBAL

  • "Streptomyces rosa subsp.notoensis"OS-3966株が生産する新規nanaomycin類縁体に関する研究

    松尾 洋孝, 宮野 怜, 野口 吉彦, 武 晃, 中西 淳, 重村 克己, 廣瀬 友靖, 砂塚 敏明, 高橋 洋子, 大村 智, 中島 琢自

    日本放線菌学会大会講演要旨集   33回   133 - 133  2018.09

    J-GLOBAL

  • 海洋由来放線菌Streptomyces sp.GKU257-1が生産する新規物質GKU257-1Aの構造解析および生物活性

    稲橋 佑起, Leetanasaksakul Kantinan, 須賀 拓弥, 松尾 洋孝, 穗苅 玲, 高橋 洋子, 塩見 和朗, Thamchaipenet Arinthip, 中島 琢自, 大村 智

    日本放線菌学会大会講演要旨集   33回   134 - 134  2018.09

    J-GLOBAL

  • Physicochemical screeningによる新規な微生物代謝産物の発掘

    中島 琢自

    バイオサイエンスとインダストリー   76 ( 4 ) 300 - 301  2018.07

    J-GLOBAL

  • Physicochemical screeningによる新規二次代謝産物の探索

    中島 琢自

    日本放線菌学会誌   32 ( 1 ) 6 - 8  2018.06

  • 薬剤感受性出芽酵母を用いた抗真菌薬シード化合物の探索

    坂井克行, 廣瀬友靖, 岩月正人, 知念拓実, 木村徹, 須賀拓弥, 野中健一, 中島琢自, 砂塚敏明, 臼井健郎, 浅見行弘, 大村智, 塩見和朗

    日本農芸化学会大会講演要旨集(Web)   2018  2018

    J-GLOBAL

  • 放線菌二次代謝産物の物理化学的性状を指標としたphysicochemical screeningによる新規物質の探索

    中島琢自, 宮野怜, 松尾洋孝, 松尾洋孝, 中西淳, 高橋洋子, 大村智

    日本農芸化学会大会講演要旨集(Web)   2018  2018

    J-GLOBAL

  • Physicochemical screeningによる糸状菌由来新規アルカロイドの探索-生産培地の検討と二次代謝産物の解析-

    宮野怜, 松尾洋孝, 野中健一, 塩見和朗, 高橋洋子, 大村智, 中島琢自

    日本農芸化学会大会講演要旨集(Web)   2018  2018

    J-GLOBAL

  • Streptomyces griseus IFO13350におけるイミニマイシン類の生合成解析

    堤隼馬, 勝山陽平, 手塚武揚, 宮野怜, 稲橋佑起, 高橋洋子, 中島琢自, 大西康夫

    日本農芸化学会大会講演要旨集(Web)   2018  2018

    J-GLOBAL

  • カテキンの光酸化を介した殺菌活性と光酸化機序の解明-その2-

    宍戸駿一, 宮野怜, 中島琢自, 松尾洋孝, 岩月正人, 中村圭祐, 菅野太郎, 江草宏, 庭野吉己

    日本防菌防黴学会年次大会要旨集   45th  2018

    J-GLOBAL

  • Streptomyces griseus IFO13350におけるイミニマイシン類の生合成研究

    堤隼馬, 勝山陽平, 手塚武揚, 宮野怜, 稲橋佑起, 高橋洋子, 中島琢自, 大西康夫

    日本放線菌学会大会講演要旨集   33rd   133 - 133  2018

    J-GLOBAL

  • エルゴステロール樹脂を用いた新規物質の探索

    伊豆田 祥子, 宮野 怜, 松本 厚子, 三浦 宏美, 野中 健一, 高橋 洋子, 大村 智, 中島 琢自

    日本放線菌学会大会講演要旨集   32回   96 - 96  2017.09

    J-GLOBAL

  • 植物分離放線菌株Allostreptomyces sp.K12-0794株が生産する新規物質について

    須賀 拓弥, 木村 徹, 廣瀬 友靖, 稲橋 佑起, 岩月 正人, 武 晃, 野中 健一, 松本 厚子, 砂塚 敏明, 塩見 和朗, 高橋 洋子, 大村 智, 中島 琢自

    日本放線菌学会大会講演要旨集   32回   97 - 97  2017.09

    J-GLOBAL

  • Actinomycetospora sp.YM25-058株が生産する新規骨格物質tatemasporineに関する研究

    木村 徹, 須賀 拓弥, 森 祥子, 菅原 孝太郎, 稲橋 佑起, 塩見 和朗, 高橋 洋子, 大村 智, 中島 琢自

    日本放線菌学会大会講演要旨集   32回   102 - 102  2017.09

    J-GLOBAL

  • 顕微ラマン分光法を用いた微生物内における生理活性物質のin situ検出

    宮岡 理美, 安藤 正浩, 細川 正人, 中島 琢自, 松本 厚子, 高橋 洋子, 濱口 宏夫, 竹山 春子

    日本生物工学会大会講演要旨集   平成29年度   162 - 162  2017.08

    J-GLOBAL

  • 顕微ラマン分光法と多変量スペクトル分解法を組み合わせたペニシリンのin situ検出

    吉田 雅駿, 宮岡 理美, 安藤 正浩, 中島 琢自, 野中 健一, 高橋 洋子, 濱口 宏夫, 竹山 春子

    日本生物工学会大会講演要旨集   平成29年度   257 - 257  2017.08

    J-GLOBAL

  • 抗トリパノソーマ活性を有するMangromicin Aの全合成と絶対立体構造の決定

    高田 拓和, 山田 健, 廣瀬 友靖, 石原 拓真, 中島 琢自, 高橋 洋子, 大村 智, 砂塚 敏明

    日本薬学会年会要旨集   137年会 ( 2 ) 125 - 125  2017.03

    J-GLOBAL

  • アゾキシ天然物Jietacinのバイオイソスターを考慮した類縁体の合成

    菅原 章公, 久保 雅彦, 廣瀬 友靖, 矢作 恭一, Welz Claudia, Mertens Cristina, Kobberling Johannes, 中島 琢自, 高橋 洋子, 大村 智, 砂塚 敏明

    日本薬学会年会要旨集   137年会 ( 2 ) 234 - 234  2017.03

    J-GLOBAL

  • 顕微ラマン分光法と多変量スペクトル分解法によるペニシリンのin vivo検出

    吉田雅駿, 宮岡理美, 安藤正浩, 中島琢自, 野中健一, 松本厚子, 高橋洋子, 竹山春子

    マリンバイオテクノロジー学会大会講演要旨集   19th  2017

    J-GLOBAL

  • 新規トレハロース誘導体“トレハンジェリンA“はSirt1活性化を介しオートファジーを誘導する

    小坂邦男, 曽田匡洋, 田中麻美, 中島琢自, 稲橋佑起, 高橋洋子, 大村智

    日本農芸化学会大会講演要旨集(Web)   2017  2017

    J-GLOBAL

  • 薬剤感受性出芽酵母を用いたミトコンドリアを標的とする新規農薬リード化合物decatamariic acidの取得

    渡邊善洋, 須賀拓弥, 成沢里美, 横川怜美, 岩月正人, 野中健一, 中島琢自, 篠原康雄, 塩月孝博, 一丸直哉, 三芳秀人, 浅見行弘, 大村智, 塩見和朗

    日本農芸化学会大会講演要旨集(Web)   2017  2017

    J-GLOBAL

  • 糸状菌を探索源としたphysicochemical screeningによる新規物質の探索

    松尾洋孝, 野中健一, 高橋洋子, 大村智, 中島琢自

    日本農芸化学会大会講演要旨集(Web)   2017  2017

    J-GLOBAL

  • 糸状菌Pochonia sp.FKI-7537株培養液抽出物から得られた新規化合物pochoniolide AおよびBについて

    宮野怜, 松尾洋孝, 野中健一, 庭野吉己, 塩見和朗, 高橋洋子, 大村智, 中島琢自

    日本農芸化学会大会講演要旨集(Web)   2017  2017

    J-GLOBAL

  • エルゴステロール樹脂を用いた新規物質の探索

    伊豆田祥子, 宮野怜, 松本厚子, 松本厚子, 三浦宏美, 三浦宏美, 野中健一, 野中健一, 高橋洋子, 大村智, 中島琢自, 中島琢自

    日本放線菌学会大会講演要旨集   32nd  2017

    J-GLOBAL

  • Micromonosporaceae科放線菌の細胞壁アミノ酸分析と分類

    武晃, 稲橋佑起, 稲橋佑起, 中島琢自, 中島琢自, 塩見和朗, 塩見和朗, 大村智, 高橋洋子, 高橋洋子, 松本厚子, 松本厚子

    日本放線菌学会大会講演要旨集   32nd  2017

    J-GLOBAL

  • カテキンの光酸化を介した殺菌活性と光酸化機序の解明

    宍戸駿一, 宮野怜, 中島琢自, 中島琢自, 佐藤恵美子, 中村圭祐, 菅野太郎, 江草宏, 庭野吉己

    日本防菌防黴学会年次大会要旨集   44th  2017

    J-GLOBAL

  • 深海由来糸状菌を探索源としたphysichochemical screeningによる新規物質の探索

    松尾洋孝, 松尾洋孝, 野中健一, 野中健一, 長野由梨子, 藤倉克則, 高橋洋子, 大村智, 中島琢自, 中島琢自

    日本微生物生態学会大会(Web)   2017 ( 0 ) 29 - 29  2017

    DOI CiNii J-GLOBAL

  • 糸状菌Pochonia sp.FKI-7537株より得られた新規抗酸化物質pochoniolidesについて

    宮野怜, 松尾洋孝, 野中健一, 稲橋佑起, 庭野吉己, 塩見和朗, 高橋洋子, 大村智, 中島琢自

    日本微生物生態学会大会(Web)   2017 ( 0 ) 28 - 28  2017

    DOI CiNii J-GLOBAL

  • Mangromicin A with Potent Antitrypanosomal Activity; Isolation, Structure Elucidation and Asymmetric Total Synthesis

    廣瀬友靖, 廣瀬友靖, 中島琢自, 高田拓和, 岩月正人, 岩月正人, 山田健, 山田健, 落合純也, 神谷義之, 石原拓真, 長井賢一郎, 松本厚子, 松本厚子, 石山亜紀, 石山亜紀, 乙黒一彦, 塩見和朗, 塩見和朗, 高橋洋子, 砂塚敏明, 砂塚敏明, 大村智

    天然有機化合物討論会講演要旨集(Web)   59th ( 0 ) 49 - 54  2017

     View Summary

    Two new cyclopentadecane antibiotics, named mangromicins A and B, wereseparated out from the culture broth of Lechevalieria aerocolonigenes K10-0216.The chemical structures of the two novel compounds were elucidated byinstrumental analyses, including various NMR, MS and X-ray crystallography.Mangromicins A and B consist of cyclopentadecane skeletons with atetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety.Mangromicins A and B showed in vitro antitrypanosomal activity with IC50 values of 2.4 and 43.4 μg/ml, respectively. An enantioselective total synthesis of(+)-mangromicin A has also been accomplished. The tetrahydrofuran ring ofmangromicin A, possessing a tetrasubstituted carbon center, was constructed byMukaiyama-type vinylogous alkylation via a cyclic oxocarbenium intermediatederived from a γ-hydroxy ketone with ideal stereoselectivity, and the4-hydroxydihydropyrone scaffold was generated via Dieckmann condensation at alate stage of the total synthesis. The reliable asymmetric synthesis of(+)-mangromicin A has revealed the absolute configuration of naturally occurringmangromicin A.

    DOI CiNii J-GLOBAL

  • Streptomyces griseus OS-3601が生産する新規化合物iminimycin Bについて

    宮野 怜, 松尾 洋孝, 木村 徹, 岩月 正人, 佐藤 倫子, 塩見 和朗, 高橋 洋子, 大村 智, 中島 琢自

    日本放線菌学会大会講演要旨集   31回   103 - 103  2016.09

    J-GLOBAL

  • 抗トリパノソーマ活性を有するMangromicin類の全合成研究

    高田 拓和, 山田 健, 廣瀬 友靖, 中島 琢自, 高橋 洋子, 大村 智, 砂塚 敏明

    日本薬学会年会要旨集   136年会 ( 2 ) 129 - 129  2016.03

    J-GLOBAL

  • 新規トレハロース化合物trehangelinの抗老化機能に関する研究

    神谷 義之, 榎本 有希子, 中島 琢自, 高橋 洋子, 松熊 祥子, 大村 智

    日本薬学会年会要旨集   136年会 ( 2 ) 214 - 214  2016.03

    J-GLOBAL

  • 微生物二次代謝産物からのミトコンドリア標的にした農薬リード化合物の探索

    渡邊 善洋, 須賀 拓弥, 成沢 里美, 岩月 正人, 中島 琢自, 野中 健一, 塩月 孝博, 篠原 康雄, 一丸 直哉, 浅見 行弘, 三芳 秀人, 大村 智, 塩見 和朗

    日本薬学会年会要旨集   136年会 ( 3 ) 96 - 96  2016.03

    J-GLOBAL

  • 放線菌Streptomyces griseus OS-3601が生産する新規物質iminimycin A及びiminimycin Bについて

    宮野怜, 松尾洋孝, 木村徹, 浅見行弘, 岩月正人, 岩月正人, 佐藤倫子, 塩見和朗, 塩見和朗, 高橋洋子, 大村智, 中島琢自

    日本農芸化学会大会講演要旨集(Web)   2016  2016

    J-GLOBAL

  • 放線菌Lechevalieria aerocolonigenes K10-0216株が生産する新規化合物に関する研究

    木村徹, 稲橋佑起, 岩月正人, 岩月正人, 高田拓和, 谷口寿章, 塩見和朗, 塩見和朗, 高橋洋子, 大村智, 中島琢自

    日本農芸化学会大会講演要旨集(Web)   2016  2016

    J-GLOBAL

  • 海洋由来の放線菌を用いたphysicochemical screeningによる新規化合物の探索

    田島文乃, 木村徹, 岩月正人, 森山俊介, 高橋洋子, 大村智, 中島琢自

    日本農芸化学会大会講演要旨集(Web)   2016  2016

    J-GLOBAL

  • 3,4-OH-DAPおよびOH-Gluを有する放線菌Rhizocola hellebori K12-0602T株の細胞壁ペプチドグリカン構造解析

    武晃, 中島琢自, 稲橋佑起, 廣瀬友靖, 塩見和朗, 大村智, 高橋洋子, 松本厚子

    日本農芸化学会大会講演要旨集(Web)   2016  2016

    J-GLOBAL

  • 微生物二次代謝産物からのミトコンドリア標的にした農薬リード化合物の探索

    渡邊善洋, 須賀拓弥, 成沢里美, 岩月正人, 岩月正人, 中島琢自, 野中健一, 野中健一, 塩月孝博, 篠原康雄, 一丸直哉, 浅見行弘, 浅見行弘, 三芳秀人, 大村智, 塩見和朗, 塩見和朗

    日本薬学会年会要旨集(CD-ROM)   136th  2016

    J-GLOBAL

  • PCRを用いた新規aminovinylcystein系化合物生産菌の探索とその構造解析

    稲橋佑起, 松本厚子, 三浦広美, 大村智, 高橋洋子, 中島琢自

    日本放線菌学会大会講演要旨集   31st  2016

    J-GLOBAL

  • Streptomyces griseus IFO13350が生産するiminimycinの生合成に関する研究

    堤隼馬, 勝山陽平, 手塚武揚, 宮野怜, 稲橋佑起, 高橋洋子, 中島琢自, 大西康夫

    日本放線菌学会大会講演要旨集   31st  2016

    J-GLOBAL

  • 顧みられない熱帯病,トリパノソーマ症に有効なマングロマイシン類の全合成研究

    高田拓和, 山田健, 廣瀬友靖, 石原拓真, 中島琢自, 高橋洋子, 大村智, 砂塚敏明

    有機合成シンポジウム講演要旨集   110th  2016

    J-GLOBAL

  • Rhizocola hellebori K12-0602T株の細胞壁に含まれる3,4-dihydroxy-DAPおよび3-hydroxy-Gluの単離とペプチドグリカン構造解析

    武晃, 稲橋佑起, 中島琢自, 廣瀬友靖, 塩見和朗, 大村智, 高橋洋子, 松本厚子

    日本放線菌学会大会講演要旨集   31st  2016

    J-GLOBAL

  • ワイン圧搾残渣への光照射による殺菌活性と活性酸素生成-既存ポリフェノールとの比較-

    塚田愛, 塚田愛, 中島琢自, 蒲池利章, 庭野吉己

    日本防菌防黴学会年次大会要旨集   43rd  2016

    J-GLOBAL

  • ワイン圧搾残渣ポリフェノールのLC/MS解析および光照射による殺菌活性と活性酸素生成

    庭野吉己, 塚田愛, 塚田愛, 中島琢自, 蒲池利章

    日本防菌防黴学会年次大会要旨集   43rd  2016

    J-GLOBAL

  • 放線菌Streptomyces griseus OS-3601が生産する新規物質について

    宮野 怜, 松尾 洋孝, 木村 徹, 浅見 行弘, 岩月 正人, 佐藤 倫子, 塩見 和朗, 高橋 洋子, 大村 智, 中島 琢自

    日本放線菌学会大会講演要旨集   30回   48 - 48  2015.09

    J-GLOBAL

  • Actinomadura sp.K13-0306株の生産する新規物質sagamilactamの構造および生物活性

    木村 徹, 浅見 行弘, 岩月 正人, 松本 厚子, 佐藤 倫子, 塩見 和朗, 高橋 洋子, 大村 智, 中島 琢自

    日本放線菌学会大会講演要旨集   30回   60 - 60  2015.09

    J-GLOBAL

  • 北里微生物ライブラリーの構築:物質生産糸状菌の保存性と物質生産能

    三浦広美, 中島琢自, 松本厚子, 野中健一, 増間碌郎, 高橋洋子, 大村智

    日本菌学会大会講演要旨集   59th  2015

    J-GLOBAL

  • 高温可溶化メタン発酵に関する新規好熱性細菌KK2012-0012株の研究

    藥師寺佑佳, 中島琢自, 甲斐穂高, 中道隆弘, 松本厚子, 松本厚子, 高橋洋子, 高橋洋子, 石橋康弘

    日本農芸化学会大会講演要旨集(Web)   2015  2015

    J-GLOBAL

  • Micromonosporaceae科放線菌の細胞壁ペプチドグリカンの構造解析

    武晃, 中島琢自, 稲橋佑起, 大村智, 塩見和朗, 塩見和朗, 高橋洋子, 松本厚子, 松本厚子

    日本農芸化学会大会講演要旨集(Web)   2015  2015

    J-GLOBAL

  • Physicochemical Screeningを用いた希少放線菌からの新規物質の探索

    木村徹, 中島琢自, 松本厚子, 松本厚子, 岩月正人, 岩月正人, 佐藤倫子, 浅見行弘, 浅見行弘, 塩見和朗, 塩見和朗, 高橋洋子, 大村智

    日本農芸化学会大会講演要旨集(Web)   2015  2015

    J-GLOBAL

  • 新規peptaibol化合物であるFKI-6324Aは害虫AAC遺伝子組換え酵母の増殖を抑制する

    須賀拓弥, 浅見行弘, 浅見行弘, 橋本祥平, 岩月正人, 岩月正人, 野中健一, 野中健一, 中島琢自, 渡邊善洋, 松本厚子, 松本厚子, 菅原亮平, 塩月孝博, 山本武範, 篠原康雄, 一丸直哉, 村井正俊, 三芳秀人

    日本農芸化学会大会講演要旨集(Web)   2015  2015

    J-GLOBAL

  • Micromonosporaceae科放線菌の細胞壁ペプチドグリカン構造解析と分類への応用

    武晃, 中島琢自, 稲橋佑起, 塩見和朗, 塩見和朗, 高橋洋子, 大村智, 松本厚子, 松本厚子

    日本放線菌学会大会講演要旨集   30th  2015

    J-GLOBAL

  • Physicochemical Screeningによる新規化合物の探索研究-新規Nanaomycin類縁物質を例に-

    松尾洋孝, BOONSNONGCHEEP Panitch, 木村徹, 岩月正人, 佐藤倫子, 野中健一, PRATHANTURARUG Sampop, 高橋洋子, 大村智, 中島啄自

    日本放線菌学会大会講演要旨集   30th  2015

    J-GLOBAL

  • 放線菌が生産する抗結核菌物質の探索

    三浦広美, 岩月正人, 稲橋佑起, 松本厚子, 中島琢自, 塩見和朗, 高橋洋子, 大村智

    日本放線菌学会大会講演要旨集   30th  2015

    J-GLOBAL

  • 植物由来希少放線菌Polymorphospora rubra K07-0510が生産するTrehangelinの生合成研究

    稲橋佑起, 白石太郎, 松本厚子, 高橋洋子, 大村智, 葛山智久, 中島琢自

    日本放線菌学会大会講演要旨集   30th  2015

    J-GLOBAL

  • 高分解能質量分析による新規mangromicin類縁体の探索

    中島琢自, 神谷義之, 谷口貴子, 木村徹, 高橋洋子, 大村智, 谷口寿章

    日本放線菌学会大会講演要旨集   30th  2015

    J-GLOBAL

  • 抗寄生虫活性を有するアゾキシ天然物の創薬展開~培養,単離,全合成,誘導体合成および生物活性試験~

    菅原章公, 久保雅彦, 廣瀬友靖, 矢作恭一, WELZ Claudia, MERTENS Cristina, KOEBBERLING Johannes, 中島琢自, 高橋洋子, 大村智, 砂塚敏明

    メディシナルケミストリーシンポジウム講演要旨集   33rd  2015

    J-GLOBAL

  • 希少放線菌Actinomadura sp.K13-0306株が生産する二次代謝産物に関する研究

    木村 徹, 中島 琢自, 松本 厚子, 塩見 和朗, 高橋 洋子, 大村 智

    日本放線菌学会大会講演要旨集   29回   59 - 59  2014.06

    J-GLOBAL

  • 新属Rhizocola helleboriの分類学的特徴と新規放線菌の探索源としての植物の可能性

    松本 厚子, 河口 洋子, 田中 和紀, 中島 琢自, 岩月 正人, 大村 智, 高橋 洋子

    日本放線菌学会大会講演要旨集   29回   68 - 68  2014.06

    J-GLOBAL

  • 殺線虫活性を有するJietacin類の培養、単離、全合成

    久保 雅彦, 菅原 章公, 廣瀬 友靖, 角田 紀明, 高橋 洋子, 中島 琢自, 大村 智, 砂塚 敏明

    日本薬学会年会要旨集   134年会 ( 2 ) 109 - 109  2014.03

    J-GLOBAL

  • 廃棄物系バイオマスの高温可溶化メタン発酵に適した好熱性細菌の可溶化試験

    藥師寺佑佳, 中島琢自, 松本厚子, 松本厚子, 中道隆広, 甲斐穂高, 大田政史, 高橋洋子, 高橋洋子, 石橋康弘

    環境科学会年会プログラム講演要旨集   2014  2014

    J-GLOBAL

  • Mangromicin類の質量分析と新規類縁体の検出

    神谷義之, 中島琢自, 谷口貴子, 岩月正人, 高橋洋子, 高橋洋子, 谷口寿章, 大村智

    日本農芸化学会大会講演要旨集(Web)   2014  2014

    J-GLOBAL

  • 病害虫ミトコンドリアに作用する天然物リガンドの探索

    浅見行弘, 浅見行弘, 森美穂子, 森美穂子, 須賀拓弥, 岩月正人, 岩月正人, 中島琢自, 橋本祥平, 野中健一, 野中健一, 松本厚子, 松本厚子, 弓削秀隆, 増間碌郎, 高橋洋子, 高橋洋子, 管原亮平, 塩月孝博, 山本武範, 篠原康雄, 一丸直哉, 村井正俊, 三芳秀人, 大村智, 塩見和朗, 塩見和朗

    日本農芸化学会大会講演要旨集(Web)   2014  2014

    J-GLOBAL

  • 北里微生物ライブラリーの構築 II.Physicochemical screeningによる新規物質の探索

    中島琢自, 神谷義之, 松本厚子, 山地賢三郎, 岩月正人, 大村智, 高橋洋子, 高橋洋子

    日本放線菌学会大会講演要旨集   28th  2013

    J-GLOBAL

  • 北里微生物ライブラリーの構築 I.長期保存物質生産菌の保存性と物質生産性の確認

    中島琢自, 三浦広美, 松本厚子, 野中健一, 増間碌郎, 鈴木賢一, 大村智, 高橋洋子

    日本放線菌学会大会講演要旨集   28th  2013

    J-GLOBAL

  • Mangromicin類の構造解析と生物活性

    神谷義之, 中島琢自, 岩月正人, 松本厚子, 大村智, 高橋洋子, 高橋洋子

    日本放線菌学会大会講演要旨集   28th  2013

    J-GLOBAL

  • 植物から分離された希少放線菌の生産する新規物質の探索(2)

    富田智宏, 岩月正人, 奥山竜輝, 中島琢自, 松本厚子, 高橋洋子, 高橋洋子, 森美穂子, 森美穂子, 大村智, 塩見和朗, 塩見和朗

    日本農芸化学会大会講演要旨集(Web)   2013  2013

    J-GLOBAL

  • 物質生産菌の培養液ライブラリーの構築

    中島琢自, 野中健一, 増間碌郎, 鈴木賢一, 高橋洋子, 大村智

    日本農芸化学会大会講演要旨集(Web)   2013  2013

    J-GLOBAL

  • 放線菌の分離と抗生物質の探索

    乙黒 美彩, 中島 琢自, 宮道 慎二

    生物工学会誌   90 ( 8 ) 493 - 498  2012.08

    CiNii J-GLOBAL

  • 微生物培養液を用いた微生物腐食防食剤のスクリーニング

    若井暁, 中島琢自, 原山重明

    材料と環境講演集   2012  2012

    J-GLOBAL

  • 植物分離放線菌からのケミカルスクリーニングによる物質探索

    奥山竜輝, 中島琢自, 松本厚子, 大村智, 高橋洋子, 高橋洋子

    日本放線菌学会大会講演要旨集   27th  2012

    J-GLOBAL

  • 植物から分離された希少放線菌の生産する新規物質の探索

    富田智宏, 岩月正人, 奥山竜輝, 中島琢自, 松本厚子, 高橋洋子, 高橋洋子, 森美穂子, 森美穂子, 大村智, 塩見和朗, 塩見和朗

    日本農芸化学会大会講演要旨集(Web)   2012  2012

    J-GLOBAL

  • 津波で被災した海洋微生物コレクションの復旧と再構築

    笠井宏朗, 中島琢自, 勝田麻津子, 松本厚子, 野中健一, 相澤好治, 紙野圭, 関口弘志, 藤田信之

    日本農芸化学会大会講演要旨集(Web)   2012  2012

    J-GLOBAL

  • Penicillium sp.FKI-5249の生産する新規アザフィロン化合物の構造及び活性

    新妻恵, 森美穂子, 森美穂子, 岩月正人, 中島琢自, 野中健一, 増間碌郎, 増間碌郎, 大村智, 塩見和朗, 塩見和朗

    日本農芸化学会大会講演要旨集(Web)   2012  2012

    J-GLOBAL

  • Efficient Methane Fermentation System with Hydrolysis Technology Using High Temperature Aerobic Hydrolysis Bacteria

    Nakamichi Takahiro, Nakahsima Takuji, Kai Hotaka, Takemoto Naomichi, Matsuo Hideki, Kobayashi Jyun, Takahasi Yoko, Ohba Kazuhiro, Ishibashi Yasuhiro

    Journal of Environment and Safety   3 ( 1 ) 1_13 - 1_20  2012

     View Summary

    &nbsp;&nbsp;&nbsp;The methane fermentation method is often used to process organic waste such as animal manure and garbage. The method attracts much attention since it works as a technology for producing renewable energy form organic waste, which changes organic waste into biogases such as methane and carbon dioxide. However, the methane fermentation process has a problem in that it involves large amounts of wastewater because organic waste is diluted with much water. In order to solve this problem, we devised a hydrolysis techn1que using an aerobic thermophilic bacterium, Anoxybacillus sp. MU3, as a pre-treatment method in methane fermentation under an aerobic high temperature environment (80&deg;C).Solubilization of sewage sludge by strain MU3, isolated from a hot spring, was investigated as a pretreatment for the methane fermentation process. Strain MU3 could be grown at an optimum temperature of 60&deg;C.<br>&nbsp;&nbsp;&nbsp;When strain MU3 was added to sewage sludge under the high temperature condition, the water-soluble CODcr value after 48 hours improved 40% compared with sample at the start of the test. The methane fermentation reactor (effective volume: 5 cubic meters) in which the sewage grime wonderment solubilization, was used to perform methane fermentation. At a SRT (sludge retention time) of 10 days, the VSS (volatile suspended solids) removal was 65%, the amount of biogas produced was 6,300/L, and the methane content in the biogas was 64%. The biogas yield per VSS removed was 1,133.6L/kg-VSS, that is, tow times greater than that of other sewage sludge treatment facilities.

    DOI CiNii J-GLOBAL

  • 微生物代謝産物由来の抗トリパノソーマ原虫活性物質の探索研究(3)

    塚島明希, 岩月正人, 石山亜紀, 生田目幸, 橋田純子, 中島琢自, 増間碌郎, 増間碌郎, 高橋洋子, 高橋洋子, 山田陽城, 山田陽城, 乙黒一彦, 大村智

    日本薬学会年会要旨集   131st ( 2 )  2011

    J-GLOBAL

  • 沖縄県西表島土壌からの放線菌の分離と新規生物活性物質探索

    落合純也, 松本厚子, 中島琢自, 岩月正人, 大村智, 高橋洋子, 高橋洋子

    日本農芸化学会大会講演要旨集   2011  2011

    J-GLOBAL

  • 沖縄県西表島のマングローブから分離されたLechevalieria sp.K10-0216が生産する新規二次代謝産物

    落合純也, 中島琢自, 松本厚子, 岩月正人, 塩見和朗, 塩見和朗, 大村智, 高橋洋子, 高橋洋子

    日本放線菌学会大会講演要旨集   26th  2011

    J-GLOBAL

  • 希少放線菌生産抗生物質の動向

    新井 守, 中島 琢自

    日本放線菌学会誌   24 ( 2 ) 78 - 91  2010.12

    CiNii

  • 微生物増殖用培地における活性酸素種発生機構の解明

    中島琢自, 三浦広美, 松本厚子, 島田梨沙, 大村智, 高橋洋子, 高橋洋子

    日本放線菌学会大会講演要旨集   25th  2010

    J-GLOBAL

  • Research on high efficiency methane fermentation for sewage sludge by high temperature sublimation method

    Nakamichi Takahiro, Nakasima Takuji, Kai Hotaka, Takamatsu Nobue, Takahashi Youko, Ishibashi Yasuhiro

    Proceedings of the Annual Conference of Japan Society of Material Cycles and Waste Management   21st ( 0 ) 156 - 156  2010

    DOI CiNii J-GLOBAL

  • 沖縄産陸上植物及び海洋生物から単離した乳酸菌によるチロシナーゼ阻害効果

    金本昭彦, 中島琢自, 池松真也

    日本農芸化学会大会講演要旨集   2009  2009

    J-GLOBAL

  • 海洋環境に特有な放線菌の選択分離について

    増田駿平, 柴田雄次, 塩塚匡樹, 春成円十朗, 今田千秋, 小林武志, 浜田(佐藤)奈保子, 中島琢自

    マリンバイオテクノロジー学会大会講演要旨集   12th  2009

    J-GLOBAL

  • 微生物増殖培地から発生する活性酸素種に関する研究

    中島琢自, 関珠枝, 松本厚子, 三浦広美, 大村智, 高橋洋子

    日本放線菌学会大会講演要旨集   24th  2009

    J-GLOBAL

  • 伊豆赤沢海洋深層水からの有用微生物の探索

    有賀みずえ, 野村道康, 美浦孝誠, 山田勝久, 中島琢自, 加藤朋, 今田千秋, 小林武志, 濱田(佐藤)奈保子

    海洋深層水利用学会全国大会講演要旨集   13th  2009

    J-GLOBAL

  • 2Ha13 Actinomycete bacteria isolated from the sediments at coastal and offshore area of Nagasaki prefecture, Japan : diversity and biological activity

    NAKASHIMA Takuji, ANZAI Kozue, KUWAHARA Natsumi, SUZUKI Rieko, TAKESHITA Satoshi, ANDO Katsuhiko

      60th   198 - 198  2008

    CiNii J-GLOBAL

  • Streptomyces roseolilacinus NBRC 12815が産生するチロシナーゼ阻害物質

    安斎こずえ, 中島琢自, 桑原奈津美, 宮道慎二, 小牧久幸, 高木基樹, 新家一男, 原山重明, 安藤勝彦

    日本農芸化学会大会講演要旨集   2008  2008

    J-GLOBAL

  • 国内土壌から分離した放線菌のNRPS遺伝子

    小牧久幸, 大野道代, 中島琢自, 原山重明

    日本農芸化学会大会講演要旨集   2008  2008

    J-GLOBAL

  • アグリバイオ実用化・産業化研究 第6章 ラフィド藻・渦鞭毛藻等赤潮の原因となるプランクトンが産生する新規生理活性物質の機能解明及び大量生産技術の開発

    松山幸彦, 庭野吉己, 倉智麻木, 内山元子, 別府史章, 板倉茂, 赤根幸子, 影山裕子, 小田達也, 中島琢自, 金大景, 宮崎洋介, 河野雅弘, 佐藤恵美子, 目代貴之

    農林水産省農林水産技術会議事務局研究成果   ( 458 )  2008

    J-GLOBAL

  • NBRC保存放線菌と長崎海洋域より得られた放線菌の生物活性の比較

    中島琢自, 安斎こずえ, 鈴木里江子, 桑原奈津美, 宮道慎二, 竹下哲史, 安藤勝彦

    日本放線菌学会大会講演要旨集   23rd  2008

    J-GLOBAL

  • NBRC保存放線菌株の系統分類と生理活性

    安斎こずえ, 大野道代, 中島琢自, 鈴木里江子, 桑原奈津美, 田村朋彦, 小牧久幸, 宮道慎二, 原山重明, 安藤勝彦

    日本放線菌学会大会講演要旨集   23rd  2008

    J-GLOBAL

  • ハトムギ加工食品の有効性についての検討

    塚田 愛, 柴田 浩樹, 中島 琢自, 村松 毅

    日本皮膚科学会雑誌   117 ( 4 ) 713 - 713  2007.03

    J-GLOBAL

  • 微生物代謝産物の多様性

    中島琢自, 小牧久幸, 安斎こずえ, 原山重明

    日本農芸化学会大会講演要旨集   2007  2007

    J-GLOBAL

  • 食用油脂分解過程における微生物相と油脂成分の解析

    村岡陽, 中島琢自, 竹下哲史, 田平泰広, 江口博, 今川和幸, 高良真也, 武政剛弘

    廃棄物学会研究発表会講演論文集   18th ( Pt.1 ) 33 - 33  2007

     View Summary

    本研究では微生物を用いた油脂阻集器内含油排水の浄化システムを検討している。システム開発に必要な微生物を確保するため、環境試料を60検体採取した。油脂を含む液体基質を用い試料に含まれる微生物を培養し、ヘキサン抽出物質量を測定することで油脂分解能を評価した。その結果、試料番号N-001が油脂分解率18.6%と最も高い値を示した。この微生物群の油脂分解活性は前培養を2日間行った場合が最も高く,この培養液を固定化して現場に投入したところ,時間の経過とともに排水中に含まれるヘキサン抽出物質量が減少した。一方,微生物群の添加作業を中断したところ排水中に含まれるヘキサン抽出物質量が急激に増加することを確認した。この結果より環境微生物群N-001は油脂阻集器内の含油排水を浄化していることが確認できる。今後は生物相遷移と油脂成分変化の双方を考慮して食用油脂分解過程の解析を行う所存である。

    DOI CiNii J-GLOBAL

  • 1G10-2 Comparison with microbial classifications and bioactivities in microbial resources preserved at NITE

    NAKASHIMA Takuji, KUWAHARA Natsumi, ANZAI Kozue, SUZUKI Rieko, KOMAKI Hisayuki, INABA Shigeki, ONO Michiyo, PARK Ju-Young, MAYUZUMI Shinzou, YAMAMURA Hideki, HARAYAMA Shigeaki

      59th   154 - 154  2007

    CiNii J-GLOBAL

  • 渦鞭毛藻類赤潮プランクトンはスーパーオキシド消去物質を産生する

    庭野吉己, 庭野吉己, 佐藤恵美子, 河野雅弘, 松山幸彦, 金大景, 金大景, 中島琢自, 中島琢自, 小田達也

    日本水産学会大会講演要旨集   2007  2007

    J-GLOBAL

  • 赤潮プランクトンに存在する光依存性溶血毒素の細胞毒性発現機構

    宮崎洋介, 中島琢自, 金大景, 山口健一, 小田達也

    マリンバイオテクノロジー学会大会講演要旨集   10th  2007

    J-GLOBAL

  • チオエステラーゼドメインに着目したI型ポリケタイド合成酵素遺伝子の解析

    小牧久幸, 末本哲雄, 中島琢自, 原山重明

    日本放線菌学会大会講演要旨集   22nd  2007

    J-GLOBAL

  • アルギン酸オリゴマーのマウスに対するサイトカイン誘導活性

    倉智麻木, 山本美子, 小田達也, 中島琢自, 山口健一

    日本農芸化学会大会講演要旨集   2006  2006

    J-GLOBAL

  • RAW264.7細胞のNADPHオキシダーゼに対するプロジギオシン誘導体の影響

    中島琢自, 佐藤恵美子, 倉智麻木, 山口健一, 庭野吉己, 小田達也

    日本農芸化学会大会講演要旨集   2006  2006

    J-GLOBAL

  • 別府市・温泉地より単離した新規な好熱性細菌

    高松伸枝, 中島琢自, 村松毅

    日本農芸化学会大会講演要旨集   2006  2006

    J-GLOBAL

  • 酵素処理アルギン酸オリゴマーの細胞及びマウスレベルでのサイトカイン放出誘導作用

    倉智麻木, 山本美子, 中島琢自, 小田達也, 山口健一, 宮崎洋介, 村松毅

    マリンバイオテクノロジー学会大会講演要旨集   9th  2006

    J-GLOBAL

  • 赤潮プランクトンから分離された新規ポルフィリン誘導体の細胞毒性

    金大景, 宮崎洋介, 中島琢自, 山口健一, 小田達也

    化学関連支部合同九州大会・外国人研究者交流国際シンポジウム講演予稿集   43rd  2006

    J-GLOBAL

  • 赤潮プランクトンから分離された新規ポルフィリン誘導体の細胞毒性

    金大景, 宮崎洋介, 中島琢自, 山口健一, 小田達也

    化学関連支部合同九州大会・外国人研究者交流国際シンポジウム講演予稿集   43rd  2006

    J-GLOBAL

  • マクロファージと植物プランクトンにおけるスーパーオキシド生成に対するγ-proteobacteriumにより産生されるprodigiosinの効果(Effect of prodigiosin produced by γ-proteobacterium on superoxide generation in macrophage and phytoplankton)

    Nakashima Takuji, Kim Daekyung, Sato Emiko, Miyazaki Yousuke, Kurachi Maki, Yanaguchi Kenichi, Niwano Yoshimi, Oda Tatsuya

    生化学   77 ( 8 ) 824 - 824  2005.08

  • アルギン酸オリゴマーのサイトカイン放出誘導作用

    倉智麻木, 小田達也, 中島琢自, 山口健一

    日本農芸化学会関西支部講演会講演要旨集   2005  2005

    J-GLOBAL

  • 赤潮プランクトン Heterocapsa circularisquama の光依存性溶血毒素の諸性質と細胞内に存在する解毒物質を用いた赤潮防除の検討

    宮崎洋介, 中島琢自, 小田達也, 山口健一

    日本農芸化学会大会講演要旨集   2005  2005

    J-GLOBAL

  • A Search for Chitin-Binding Proteins from Wastewater Discharged during the Leaching Process of Surimi Manufacturing

    武井明, 中島琢自, 山口健一, 小田達也

    キチン・キトサン研究   11 ( 2 ) 199 - 199  2005

    CiNii J-GLOBAL

  • Isolation and Identification of a Chitin-Binding Protein from Pulps of Pokeweed (Phytolacca americana)

    山口健一, 武井明, 中島琢自, 小田達也, 石黒正恒

    キチン・キトサン研究   11 ( 2 ) 197 - 197  2005

    CiNii J-GLOBAL

  • 赤潮プランクトンに対する増殖阻害物質の感受性について

    中島琢自, 宮崎洋介, 加藤陽子, 山口健一, 小田達也

    日本農芸化学会大会講演要旨集   2005  2005

    J-GLOBAL

  • Structure-activity relationship of alginates to induce TNF-α secretion from RAW264.7 cells

    倉智麻希, 宮島千尋, 岩本佳子, 村松毅, 中島琢自, 山口健一, 小田達也

    長崎大学水産学部研究報告   ( 86 ) 11 - 16  2005

    CiNii J-GLOBAL

  • LS1-1 The marine microorganism library as resources for useful bioactivity

    Kodama Seiji, Suzuki Keiji, Matsuda Naoki, Takeshita Satoshi, Nakashima Takuji, Watanabe Masami

      33rd ( 33 ) 93 - 93  2004

    CiNii J-GLOBAL

  • Candida albicansの活性酸素産生像を捉える

    増居 茂樹, 中島 琢自, 馬島 敏郎, 久和 彰江, 仲村 健二郎, 青木 茂治

    日本医真菌学会雑誌   43 ( Suppl.2 ) 95 - 95  2002.09

    J-GLOBAL

  • 外用抗真菌剤のin vivo薬効評価試験に有用な新規培地の開発

    中島 琢自, 野沢 暁, 伊藤 隆男, 馬島 敏郎, 山口 英世

    日本医真菌学会雑誌   42 ( Suppl.1 ) 103 - 103  2001.09

    J-GLOBAL

  • 爪真菌症の新しい治療 爪白癬のin vitro評価系の作製

    中島 琢自, 野沢 暁, 伊藤 隆男, 馬島 敏郎

    日本医真菌学会雑誌   41 ( Suppl.1 ) 82 - 82  2000.10

    J-GLOBAL

  • 皮膚糸状菌に対するPR-2699(NND-502)の抗真菌活性測定法の多施設評価

    山口 英世, 内田 勝久, 小林 寅哲, 馬島 敏郎, 伊藤 隆男, 中島 琢自, 金井 和夫, 古賀 裕康, 辻 有里

    日本医真菌学会雑誌   41 ( Suppl.1 ) 114 - 114  2000.10

    J-GLOBAL

  • 海洋生物資源ライブラリーの構築 (科学技術振興事業団S)

    蓮田勝美, 市毛秀則, 太田洋子, 中島琢自

    共同研究等促進事業研究成果報告書 平成9年    1997

    J-GLOBAL

  • Influence of Amino Acids Pooled in Bacillus colistinus Koyama on External Magnetic Field.

    下山博正, 山口浩司, 吉村昇, 中島琢自, 吉田有子, 工藤行蔵

    電気学会全国大会講演論文集   1995 ( 2 )  1995

    J-GLOBAL

  • 抗菌性抗生物質Colistin 産生におよぼす磁束密度の影響

    吉田 有子, 吉村 昇, 鈴木 雅史, 中島 琢自, 工藤 行蔵

    電気化学および工業物理化学   62 ( 9 ) 892 - 893  1994

    DOI CiNii

  • Magnetism-Mediated Productivity of an Antimicrobial Agent Colistin by Bacillus colistinus DU-24-49K-5.

    吉田有子, 吉村昇, 鈴木雅史, 中島琢自, 工藤行蔵

    電気化学および工業物理化学   62 ( 9 )  1994

    J-GLOBAL

  • Effects of dc magnetic field on production of antibiotics.

    吉村昇, 下山博正, 木田正彦, 中島琢自, 山口浩司, 工藤行蔵

    電気学会マグネティックス研究会資料   MAG-94 ( 153-164 )  1994

    J-GLOBAL

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Industrial Property Rights

  • 光分解性農薬組成物

    Patent

     View Summary

    特願2004-093597

  • プロジギオシン類色素の製造方法およびそれに使用する新規な微生物

    Patent

     View Summary

    特願2004-078807

  • 微生物分離法

    Patent

     View Summary

    特願2004-040349

  • 石油類分解微生物および石油類の処理方法

    Patent

     View Summary

    特願2004-078812

  • 皮膚外用剤

    Patent

  • 紫外線吸収剤及びそれを含有する紫外線防護用の化粧料

    Patent

  • メラニン生成阻害剤及び皮膚外用剤

    Patent

  • メラニン産生抑制剤及び美白用皮膚外用剤

    Patent

  • 紫外線吸収剤及び皮膚外用剤

    Patent

  • 皮膚外用剤

    Patent

  • 2,4,6-トリヒドロキシカルコン及びそれを含有する化粧料

    Patent

  • 紫外線吸収剤及びこれを含有する化粧料

    Patent

  • 紫外線吸収剤及びこれを含有する化粧料

    Patent

  • 紫外線吸収剤及びこれを含有する化粧料

    Patent

  • 新規なヘキサヒドロジベンゾフラン誘導体、並びにそれを用いたメラニン産生抑制剤及び化粧料

    Patent

  • 抗真菌剤及びそれを含有する組成物

    Patent

  • ベンゾフェノン誘導体及びそれを含有する組成物

    Patent

  • 抗真菌剤

    Patent

  • 抗真菌剤

    Patent

  • 抗真菌剤

    Patent

  • 抗真菌剤

    Patent

  • 新規N-ベンジルベンズアミド誘導体

    Patent

  • 抗真菌剤

    Patent

  • 抗真菌剤

    Patent

  • 抗真菌剤及びその製造方法

    Patent

  • アミン誘導体

    Patent

  • アミン誘導体

    Patent

  • アミン誘導体およびその製造方法

    Patent

  • 含硫黄抗真菌剤

    Patent

  • 抗真菌剤

    Patent

  • 抗真菌剤

    Patent

  • 芳香族抗真菌剤

    Patent

  • 芳香族抗真菌剤

    Patent

  • 抗真菌剤及びそれを含有する組成物

    Patent

  • 芳香族抗真菌剤

    Patent

  • 新規化合物及びその製造法

    Patent

  • 爪用の抗真菌剤の評価法

    Patent

  • 爪用の抗真菌剤の評価法

    Patent

  • 抗真菌剤の評価法

    Patent

  • 抗真菌医薬組成物

    Patent

  • 爪の切片の調整法

    Patent

  • 抗真菌医薬組成物

    Patent

  • 抗微生物剤の評価法

    Patent

  • 抗真菌医薬組成物

    Patent

  • 抗真菌医薬組成物

    Patent

  • 医薬組成物

    Patent

  • 水質浄化装置

    Patent

  • サイトカイン分泌促進剤

    Patent

  • 熱耐性プロテアーゼを産生する新規微生物

    Patent

  • NADPHオキシダーゼ阻害剤

    Patent

  • メラニン産生抑制剤、抗酸化剤、抗炎症剤、皮膚外用剤及び飲食品

    Patent

  • 新規マングロマイシン化合物及びその製造方法

    Patent

  • 新規光線過敏症抑制剤トレハンジェリン物質及びその製造法

    Patent

  • 化粧料または皮膚外用剤

    Patent

  • 新規マングロマイシン化合物及びそれを含有するフリーラジカル消去剤

    Patent

  • 新規なグルコースデヒドロゲナーゼ

    Patent

  • 皮膚バリア機能改善効果を有する放線菌培養物

    Patent

  • 新規サガミラクタム物質およびその製造法

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  • トレハンジェリンの製造法

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  • エルゴステロール修飾担体、抗真菌剤の候補物質のスクリーニング方法、及び抗真菌剤の原料の精製方法

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  • 上皮間葉転換誘導細胞阻害剤

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  • 新規ポコニオライド化合物及びその使用

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  • 新規フザラミン物質を有効成分とする白血病細胞増殖抑制剤

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Awards

  • ポスター賞

    2019.09   日本放線菌学会  

  • 富士電機賞

    2014.09   環境化学会   廃棄物系バイオマスの高温可溶化メタン発酵に適した好熱性細菌の可溶化試験

  • 日本農芸化学研究企画賞

    2013.03   日本農芸化学会  

  • ポスター賞

    2009.07   日本放線菌学会  

  • 優秀賞

    2009.03   バイオビジネスコンペJAPAN  

  • 優秀ポスター賞

    2002.09   日本医真菌学会  

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Research Projects

  • Elucidation of relationship between plants and related actinomycetes

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Project Year :

    2022.04
    -
    2025.03
     

  • 複合生物培養法による難培養植物内生放線菌の分離と生育因子の解明

    日本学術振興会  科学研究費助成事業 基盤研究(C)

    Project Year :

    2018.04
    -
    2020.03
     

    松本 厚子, 中島 琢自, 稲橋 佑起

     View Summary

    低温の熱処理(60C, 1h)を加えた植物の根サンプルから、通常法により分離した2属6株の放線菌菌体混合液を分離培地に加え、メンブレンフィルターで仕切り、その上で同植物サンプルからの分離を試みた。
    分離株は16S rRNA 遺伝子部分塩基配列(約600bp)から属を推定し、菌体混合液を加えない対照群と比較した。共培養により分離した32株は10属 (Streptomyces, Microbacterium, Hamadaea, Polymorphospora, Amycolatopsis, Actinomadura, Actinoplanes, Microbispora, Sphaerisporangium, Cellulosimicrobium)に、対照群からは14株分離し7属 (Streptomyces, Dactylosporangium, Micromonospora, Actinoplanes, Microbispora, Sphaerisporangium, Cellulosimicrobium)に分類された。このうち5属は共培養のみから、2属は対照群のみから分離されており、共培養による影響が観察された。本方法は未利用放線菌の新しい分離法の一つと位置付けられる。今後、共培養に用いる菌株や量などの検討により未利用放線菌の分離拡大が可能であると同時に生育因子の解明が期待される。
    一方、同サンプルのメタゲノム解析からは Actinobacteria 門では Nocardioidaceae 科、Streptomyces 属、Micromonosporaceae 科、Actinosynnemataceae 科、Curtobacterium 属 が50% を占めるものの、その多くは分離されていないことが明らかで、分離法の重要性を裏付けた。

  • Search for new ergosterol binding amphiphilic compounds

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Project Year :

    2017.04
    -
    2020.03
     

    Nakashma Takuji

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    Ergosterol is an essential component for fungal growth. we developed silica-binding ergosterol (ES silica) resin and searched for natural products interacting with ergosterol from actinomycete culture broths. And 24 natural products were deduced as new ones. Dipyrimicins and Dietziamide C, new compounds interacted with ES silica, were discovered from actinomycete culture extracts. Dipyrimicin B possesses a 2,2′-dipyridine core skeleton with amide groups. The amide group in dipyrimicin B could be the primary factor involved in the interaction with ES silica. Dietziamide C is a unique structure that possesses a N,N,N-trimethylpropan-1-aminium at the center of tetramic acid dimer. It was suggested that ES silica interacts with microbial alkaloids.

  • 微生物代謝産物からの抗結核物質の探索と作用点の解明

    日本学術振興会  科学研究費助成事業 基盤研究(C)

    Project Year :

    2016.04
    -
    2018.03
     

    三浦 広美, 松本 厚子, 中島 琢自, 野中 健一, 稲橋 佑起

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    抗結核薬の新たな標的として、細菌のペプチドグリカンの構成成分であるジアミノピメリン酸 (DAP) の合成経路に着目した先行研究(「微生物二次代謝産物からの新抗結核薬の探索」平成26-27年度、挑戦的萌芽研究)にてStreptomyces sp. K12-0214の培養液を候補として見出し、本研究で活性物質の単離・精製を進めた。
    本活性物質は水溶性で、通常単離に汎用されているODS、silica、HP20などの樹脂では分離が困難であったため、水溶性物質の単離に応用できそうな種々の樹脂と溶出条件を用いて精製条件の検討を行った。その結果、Arg修飾silica樹脂を用いて親水性相互作用クロマトグラフィー(Hydrophilic Interaction Chromatography=HILIC)で溶出することにより、比活性が20倍に上昇した画分を得ることができた。 この画分をBio-gel P-10を用いてゲルろ過クロマトグラフィーにて分画したところ、さらに比活性が上昇した画分を得ることができた。溶出容量からこの活性物質は分子量>700であると推測された。このBio-gel P-10活性画分についてNMR測定を試みたが、複数の物質が混在しており構造の推定には至らなかった。過去の文献の情報より、有機酸の可能性が考えられたため、種々の標品 (乳酸、リンゴ酸、酒石酸、クエン酸、ピルビン酸、コハク酸)とともに薄層クロマトグラフィーを行って比較したが、いずれとも一致しなかった。
    これまでに得られた知見より、本活性物質は水溶性物質で分子量は700より大きく、塩基性条件下で活性が減弱する。さらに抗菌スペクトルの特徴(M. smegmatis および E. coli に抗菌活性を示し、S. aureus には抗菌活性を示さない)からも、既存の抗結核薬や有機酸とは異なる物質であることが強く示唆された。

  • Development of isolation method for endophytic actinomycetes using plant model and search for microbial resources

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Project Year :

    2015.04
    -
    2018.03
     

    Matsumoto Atsuko, TAKAHASHI Yoko, SHIOMI Kazuro

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    There are many untapped endophytic actiomycetes. In order to isolate and culture them as source of new bioactive compounds, new isolation method using cultured cell of plant was developed. Endophytic actinomycete strain, which requires cultured cell of plant for growth was isolated by this method.
    It was showed by taxonomic study that isolated endophytic actinomycetes were three new species belonging the genus Kibdelosporangium, and the 22-membered macrolides, hamuramicin was found in the cultured broth of endophytic actinomycetes Allostreptomyces sp. K12-0794.

  • -

    Project Year :

    2016
    -
    2018
     

  • Screening of anti-tuberculosis substances produced by microorganism

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Project Year :

    2014.04
    -
    2016.03
     

    Miura Hiromi, MATSUMOTO Atsuko, NAKASHIMA Takuji, TAKAHASHI Yōko, SHIOMI Kazuro, IWATSUKI Masato

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    To discover anti-tuberclosis drugs with a new mechanisms of action, we invented simple screening system that is targeted to biosynthesis pathway of diaminopimelate (DAP). We screened approximately 9,600 culture broths of actinomycete and fungi. As a result, we found anti-mycobacterium substance produced by Streptomyces sp. K12-0214. This substance is water-soluble, irreversibly inactivated under basic condition. Anti-microbial spectrum of this material was different from that of existing drug isoniadide and rifampicin.

  • 海洋微生物ライブラリーの構築

    Project Year :

    2002
    -
    2005
     

  • 赤潮プランクトンの活性酸素産生阻害物質の探索

  • 生理機能を有した微生物の探索

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