NAKASHIMA, Takuji

写真a

Affiliation

Affiliated organization, Research Innovation Center

Job title

Senior Researcher(Professor)

Concurrent Post 【 display / non-display

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

Education 【 display / non-display

  •  
    -
    1991

    Nagasaki University  

Degree 【 display / non-display

  • Nagasaki University   pharmacy

Research Experience 【 display / non-display

  • 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 【 display / non-display

  • 2021.03
    -
    Now

    マリンバイオテクノロジー学会

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    日本放線菌学会

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    日本生物工学会

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    日本農芸化学会

 

Research Areas 【 display / non-display

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

Research Interests 【 display / non-display

  • 応用微生物学、生物活性、天然物化学、分析化学、生化学

Papers 【 display / non-display

  • 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    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

  • 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

  • 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

  • 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]

     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]

     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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Misc 【 display / non-display

  • 琥珀と微生物由来の生物活性物質のPPM1A活性化作用とRBL-2H3細胞での脱顆粒抑制活性との関連性

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

    日本生化学会大会プログラム・講演要旨集   93回   [2Z05 - 697)]  2020.09

    J-GLOBAL

  • Study on skin barrier function of trehangelin, a new trehalose compound

    神谷義之, 横田麻美, 鈴木民恵, 桜井哲人, 中島琢自, 高橋洋子, 大村智

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

    J-GLOBAL

  • Detection of Mangromicin analogs by using Raman microspectroscopy

    向島諒, 安藤正浩, 安藤正浩, ASHOK Samuel, 中島琢自, 高橋洋子, 松本厚子, 竹山春子, 竹山春子, 竹山春子, 竹山春子

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

    J-GLOBAL

  • In situ Detection of Penicillin and Avermectin in Microbes by Raman Microspectroscopy and Multivariate Analysis

    堀井俊平, 堀井俊平, 安藤正弘, 安藤正弘, 中島琢自, 中島琢自, ASHOK Samuel, 松本厚子, 高橋洋子, 竹山春子, 竹山春子, 竹山春子, 竹山春子

    日本農芸化学会大会講演要旨集(Web)   2020  2020

    J-GLOBAL

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

    稲橋佑起, 中島琢自, 葛山智久

    Institute for Fermentation, Osaka. Research Communications   ( 34 ) 121 - 128  2020

    CiNii J-GLOBAL

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Industrial Property Rights 【 display / non-display

  • 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

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Awards 【 display / non-display

  • 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  

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Research Projects 【 display / non-display

  • 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

    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

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2017.04
    -
    2020.03
     

    Nakashma Takuji

     View Summary

    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

    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

     View Summary

    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

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2015.04
    -
    2018.03
     

    Matsumoto Atsuko, TAKAHASHI Yoko, SHIOMI Kazuro

     View Summary

    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
     

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Syllabus 【 display / non-display