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Construction of a fraction lirary with wide diversity and application for discovery of new bioactive compounds

Research Project

Project/Area Number 17K07784
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bioorganic chemistry
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Nogawa Toshihiko  国立研究開発法人理化学研究所, 環境資源科学研究センター, 研究員 (40462717)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords微生物代謝産物 / フラクションライブラリー / スペクトルデータベース / 新規化合物 / 活性物質 / 微生物二次代謝産物 / 生理活性物質 / 天然物
Outline of Final Research Achievements

I constructed a method to search and isolate structurally and biologically interesting secondary metabolites efficiently from microbes by the following 4 tasks: (1) construction of a fraction library with high diversity, (2) construction of spectral database based on LC/MS analysis, (3) evaluation of biological activities, and (4) search and isolation of new active metabolites. As the results, a fraction library was prepared from culture broths of 19 fungi by 3 different culture conditions. The library was analyzed by LC/MS for constructing a database and evaluated its biological activities including cytotoxicity and antimicrobial activities. Based on the database search coupled with activity tests, some interesting compounds were identified. The results were presented in conferences and published in academic journals. I confirmed the efficiency and importance of the method for isolating new active compounds from microbes.

Academic Significance and Societal Importance of the Research Achievements

微生物二次代謝産物は、多様な構造と生理活性から創薬資源として重要である。しかし、精製の手間や量の確保の難しさ、最近では新規の構造や活性を有する化合物発見の難しさなどからも研究の継続が困難になっている。大手製薬企業なども同様の状況である。本課題では、これら欠点を解消するため、微生物本来の二次代謝産物生産能を活用するとともに、従来法では見落とされていた微量代謝産物にもフラクションライブラリーの手法を応用することで注目した。ここで確立した方法の活用により、医薬品などのシード化合物およびバイオプローブの創出につなげることが期待できる。また、限りある微生物資源を有効活用することにおいても重要である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (51 results)

All 2020 2019 2018 2017

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 1 results) Presentation (36 results) (of which Int'l Joint Research: 6 results) Book (1 results)

  • [Journal Article] Biosynthetic gene cluster identification and biological activity of lucilactaene from Fusarium sp. RK97-942020

    • Author(s)
      Kato Sho、Motoyama Takayuki、Futamura Yushi、Uramoto Masakazu、Nogawa Toshihiko、Hayashi Toshiaki、Hirota Hiroshi、Tanaka Akira、Takahashi-Ando Naoko、Kamakura Takashi、Osada Hiroyuki
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 84 Issue: 6 Pages: 1303-1307

    • DOI

      10.1080/09168451.2020.1725419

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of secondary metabolite production by hygromycin B and identification of the 1233A biosynthetic gene cluster with a self-resistance gene2020

    • Author(s)
      Kato Sho、Motoyama Takayuki、Uramoto Masakazu、Nogawa Toshihiko、Kamakura Takashi、Osada Hiroyuki
    • Journal Title

      The Journal of Antibiotics

      Volume: - Issue: 7 Pages: 475-479

    • DOI

      10.1038/s41429-020-0295-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure and biological activity of metarhizin C, a new stereoisomer of BR-050 from a fungus Tolypocladium album RK17-F00072019

    • Author(s)
      Nogawa T., Kawatani M., Okano A., Futamura Y., Aono H., Shimizu T., Kato N., Kikuchi H., and Osada H.
    • Journal Title

      J. Antibiot.

      Volume: 72 Issue: 12 Pages: 996-1000

    • DOI

      10.1038/s41429-019-0229-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nocardamin glucuronide, a new member of the ferrioxamine siderophores isolated from the ascamycin-producing strain Streptomyces sp. 80H647.2019

    • Author(s)
      Lopez JAV, Nogawa T, Futamura Y, Shimizu T, Osada H.
    • Journal Title

      J Antibiot

      Volume: 72 Issue: 12 Pages: 991-995

    • DOI

      10.1038/s41429-019-0217-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-cholinesterase potential of diverse botanical families from Malaysia: Evaluation of crude extracts and fractions from liquid-liquid extraction and acid-base fractionation2019

    • Author(s)
      Amir Rawa Mira Syahfriena、Hassan Zurina、Murugaiyah Vikneswaran、Nogawa Toshihiko、Wahab Habibah A.
    • Journal Title

      Journal of Ethnopharmacology

      Volume: 245 Pages: 112160-112160

    • DOI

      10.1016/j.jep.2019.112160

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of Nectriapyrone Biosynthesis in the Rice Blast Fungus Pyricularia oryzae by Disturbance of the Two-Component Signal Transduction System2019

    • Author(s)
      Motoyama Takayuki、Nogawa Toshihiko、Hayashi Toshiaki、Hirota Hiroshi、Osada Hiroyuki
    • Journal Title

      ChemBioChem

      Volume: 20 Issue: 5 Pages: 693-700

    • DOI

      10.1002/cbic.201800620

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Construction of a potato fraction library for the investigation of functional secondary metabolites2019

    • Author(s)
      Nogawa T, Futamura Y, Okano A, Suto M, Nakamura J, Ishihara K, Osada H.
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 83 Issue: 1 Pages: 65-75

    • DOI

      10.1080/09168451.2018.1525273

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bioenergetic and proteomic profiling to screen small molecule inhibitors that target cancer metabolisms.2019

    • Author(s)
      Futamura Y, Muroi M, Aono H, Kawatani M, Hayashida M, Sekine T, Nogawa T, Osada H.
    • Journal Title

      Biochim Biophys Acta Proteins Proteom.

      Volume: 1867 Issue: 1 Pages: 28-37

    • DOI

      10.1016/j.bbapap.2018.06.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Control of the stereochemical course of [4+2] cycloaddition during trans-decalin formation by Fsa2-family enzymes2018

    • Author(s)
      Kato N, Nogawa T, Takita R, Kinugasa K, Kanai M, Uchiyama M, Osada H, Takahashi S
    • Journal Title

      Angew Chem Int Ed Engl

      Volume: 57 Issue: 31 Pages: 9754-9758

    • DOI

      10.1002/anie.201805050

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Wakodecalines A and B, new decaline metabolites isolated from a fungus Pyrenochaetopsis sp. RK10-F0582018

    • Author(s)
      Nogawa T, Kato N, Shimizu T, Okano A, Futamura Y, Takahahi S, Osada H
    • Journal Title

      The Journal of Antibiotica

      Volume: 71 Issue: 1 Pages: 123-128

    • DOI

      10.1038/ja.2017.103

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Kinanthraquinone, a new anthraquinone carboxamide isolated from Streptomyces reveromyceticus SN-593-442018

    • Author(s)
      Takagi H, Nogawa T, Futamura Y, Takahashi S, Osada H
    • Journal Title

      The Journal of Antibiotics

      Volume: 71 Issue: 4 Pages: 480-482

    • DOI

      10.1038/s41429-017-0020-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] RK-144171, a new benadrostin derivative produced by Streptomyces sp. RK88-1441.2017

    • Author(s)
      Jang JP, Takahashi S, Futamura Y, Nogawa T, Jang JH, Ahn JS, Osada H
    • Journal Title

      J Antibiot

      Volume: 70 Issue: 1 Pages: 102-104

    • DOI

      10.1038/ja.2016.65

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Octaminomycins A and B, Cyclic Octadepsipeptides Active against Plasmodium falciparum.2017

    • Author(s)
      Jang JP, Nogawa T, Futamura Y, Shimizu T, Hashizume D, Takahashi S, Jang JH, Ahn JS, Osada H
    • Journal Title

      J Nat Prod

      Volume: 80 Issue: 1 Pages: 134-140

    • DOI

      10.1021/acs.jnatprod.6b00758

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Trachyspic acid 19-butyl ester, a new inhibitor of Plk1 polo box domain-dependent recognition from uncharacterized fungus RKGS-F2684.2017

    • Author(s)
      Nogawa T, Ogita N, Futamura Y, Negishi S, Watanabe N, Osada H
    • Journal Title

      J Antibiot

      Volume: 70 Issue: 5 Pages: 705-707

    • DOI

      10.1038/ja.2016.167

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 放線菌異種発現によるverticilactam新規類縁体の生産と単離・構造決定2020

    • Author(s)
      野川 俊彦、寺井 淳高、新家 一男、池田 治生、高橋 俊二、長田 裕之
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A microbial broth library and new compounds from microbes2019

    • Author(s)
      Nogawa Toshihiko, Osada Hiroyuki
    • Organizer
      URICAS Symposium 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糸状菌からのデカリン含有化合物の単離と構造2019

    • Author(s)
      野川俊彦
    • Organizer
      理研シンポジウム:デカリン化合物の化学合成と生合成
    • Related Report
      2019 Annual Research Report
  • [Presentation] イネいもち病菌における二次代謝活性化2019

    • Author(s)
      本山高幸、野川俊彦、石井友彬、尹忠銖、長田裕之
    • Organizer
      第61回天然有機化合物討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Acetylcholinesterase inhibitors from malaysian plants2019

    • Author(s)
      Mira Syahfriena Amir Rawa, Nogawa Toshihiko, Habibah A. Wahab, Osada Hiroyuki
    • Organizer
      日本生薬学学会 第66回年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] イネいもち病菌における二次代謝活性化2019

    • Author(s)
      本山 高幸、野川 俊彦、尹 忠銖、長田 裕之
    • Organizer
      第10回発行学フォーラム
    • Related Report
      2019 Annual Research Report
  • [Presentation] イネいもち病菌におけるnectriapyrone類の生産誘導と生理機能解析2019

    • Author(s)
      本山 高幸、野川 俊彦、長田 裕之
    • Organizer
      19回糸状菌分子生物学研究会コンファレンス
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新しいタイプの二次代謝酵素TAS1のホモログを活用した新規生理活性天然化合物の発掘2019

    • Author(s)
      本山 高幸、野川 俊彦、清水 猛、川谷 誠、二村 友史、尹 忠銖、長田 裕之
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 放線菌由来抗生物質により生産誘導されるイネいもち病菌二次代謝産物の生理機能解析2019

    • Author(s)
      古山 祐貴、本山 高幸、野川 俊彦、鎌倉 高志、長田 裕之
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A microbial broth library and new compounds from microbes2019

    • Author(s)
      Toshihiko Nogawa, Hiroyuki Osada
    • Organizer
      URICAS Synposium 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Functional analysis of Fsa2-family decalin synthase responsible for stereoselective [4+2] cycloaddition2019

    • Author(s)
      Naoki Kato, Toshihiko Nogawa, Ryo Takita, Kiyomi Kinugasa, Hiroyuki Osada, Shunji Takahashi
    • Organizer
      2nd China-Japan Joint Symposium on Natural Product Biosynthesis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] がん細胞に活性酸素種産生を誘導する化合物RKN9055の発見と作用解析2019

    • Author(s)
      河村 達郎、二村 友史、室井 誠、川谷 誠、Erchang SHANG、Petra JANNING、近藤 恭光、野川 俊彦、Slava ZIEGLER、渡辺 信元、Herbert WALDMANN、長田 裕之
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 糸状菌RK17-F0007より単離したBR-050立体異性体の構造と活性評価2019

    • Author(s)
      野川 俊彦、川谷 誠、岡野 亜紀子、青野 晴美、清水 猛、長田 裕之
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Isolation of Secondary Metabolites from Streptomyces sp. Cultured in Different Media2019

    • Author(s)
      Lopez Julius, Nogawa Toshihiko, Futamura Yushi, Shimizu Takeshi, Hashizume Daisuke, Osada Hiroyuki
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 糸状菌Pleosporales sp. RKB3564の生産するpyrrolizilactone生合成経路の解析2019

    • Author(s)
      廣澤 早香、加藤 直樹、野川 俊彦、衣笠 清美、高橋 俊二、長田 裕之
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] イネいもち病菌のネクトリアピロン類の生産誘導と生理機能解析2019

    • Author(s)
      本山高幸、野川 俊彦、長田裕之
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Pyricularia oryzaeにおけるpyriculol類生合成に関わるNADPH-dependent aldo/keto reductase (PYR7) の研究2019

    • Author(s)
      古山祐貴 、本山高幸、野川俊彦、清田洋正、鎌倉高志、長田裕之
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Tolypocladium albumにおいてNPD938によって生産誘導されるpyridoxatinとF14329の生合成と生産制御の解析2019

    • Author(s)
      石井友彬、本山高幸、野川 俊彦、鎌倉高志、長田裕之
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Kinanthraquinone生合成遺伝子クラスターの解析2018

    • Author(s)
      高尾 理沙、鬼頭 奈央子、高木 海、野川 俊彦、長田 裕之、高橋 俊二
    • Organizer
      第33回日本放線菌学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] じゃがいもフラクションライブラリーを利用した新規機能性成分の探索2018

    • Author(s)
      野川俊彦、二村 友史、岡野 亜紀子、須藤 麻里、中村 純也、石原 克之、長田 裕之
    • Organizer
      第60回天然有機化合物討論会
    • Related Report
      2018 Research-status Report
  • [Presentation] [4+2]環化付加反応におけるデカリン合成酵素Fsa2の機能解析2018

    • Author(s)
      加藤 直樹、野川 俊彦、滝田 良、衣笠 清美、金井 美紗衣、内山 真伸、長田 裕之、高橋 俊二
    • Organizer
      第60回天然有機化合物討論会
    • Related Report
      2018 Research-status Report
  • [Presentation] デカリン合成酵素遺伝子置換による非天然型天然物誘導体の創出2018

    • Author(s)
      加藤直樹、野川俊彦、衣笠清美、長田裕之、高橋俊二
    • Organizer
      第18回糸状菌分子生物学コンファレンス
    • Related Report
      2018 Research-status Report
  • [Presentation] New approarch to search and isolate novel secondary metabolites from microbes for a chemical biology study2018

    • Author(s)
      Nogawa T, Osada H
    • Organizer
      International Symposium on Himalayan Biodiversity Bioresources
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 糸状菌Prenochaetopsis sp. RK10-F058より単離した新規デカリン骨格含有二次代謝産物wakodecaline Cの構造2018

    • Author(s)
      野川俊彦、加藤直樹、清水猛、岡野亜紀子、二村友史、高橋俊二、長田裕之
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] がん代謝阻害剤スクリーニングと呼吸阻害作用解析2018

    • Author(s)
      室井誠、二村友史、青野晴美、川谷誠、関根朋美、野川俊彦、林田莉奈、長田裕之
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] がん代謝研究を加速するオミックス解析基盤の構築2018

    • Author(s)
      佐竹華子、二村友史、室井誠、野川俊彦、川谷誠、井本正哉、長田裕之
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] がん代謝を阻害するプレニルフラボノイドの作用機序解析2018

    • Author(s)
      二村友史、青野晴美、佐竹華子、室井誠、川谷誠、野川俊彦、井本正哉、長田裕之
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 立体選択的デカリン形成を担うFsa2ファミリーDiels-Alderaseの機能解析2018

    • Author(s)
      加藤直樹、野川俊彦、衣笠清美、高橋俊二、長田裕之
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] イネいもち病菌におけるpyriculol類生合成関連aldo/keto reductase遺伝子の機能解析2018

    • Author(s)
      古山祐貴、本山高幸、野川俊彦、清田洋正、鎌倉高志、長田裕之
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規アントラキノンkinanthraquinoneの同定と生物活性評価2018

    • Author(s)
      高木海、野川俊彦、二村友史、長田裕之、高橋俊二
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] じゃがいもの新規機能性成分探索に向けたフラクションライブラリーの作製2017

    • Author(s)
      野川俊彦、二村友史、岡野亜紀子、石原克之、須藤麻里、伊藤政喜、長田裕之
    • Organizer
      日本農芸化学会2017年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] じゃがいもフラクションライブラリーを用いた抗糖化活性の検討2017

    • Author(s)
      須藤麻里、吉澤潮梨、石原克之、野川俊彦、二村友史、岡野亜紀子、長田裕之
    • Organizer
      日本農芸化学会2017年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] イネいもち病菌におけるピリクロール類生合成に関わるFAD依存性モノオキシゲナーゼ遺伝子の解析2017

    • Author(s)
      古山祐貴、本山高幸、鎌倉高志、野川俊彦、長田裕之
    • Organizer
      日本農芸化学会2017年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Application of a fraction library for new mwtabolites search2017

    • Author(s)
      Nogawa T, Okano A, Futamura Y, Shimizu T, Watanabe N, Takahashi S, Osada H
    • Organizer
      3rd KRIBB-RIKEN Chamical Biology Joint Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fsa2-family Diels-Alderases are responsible for the stereoselective decaline formation2017

    • Author(s)
      Kato N, Nogawa T, Kinugasa K, Takahashi S, Osada H
    • Organizer
      3rd KRIBB-RIKEN Chamical Biology Joint Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 糸状菌Pyrenochaetopsis sp. RK10-F058より単離した新規デカリン骨格含有二次代謝産物の構造2017

    • Author(s)
      野川俊彦、加藤直樹、清水猛、岡野亜紀子、二村友史、高橋俊二、長田裕之
    • Organizer
      第59回天然有機化合物討論会
    • Related Report
      2017 Research-status Report
  • [Book] Cutting-Edge Organic Synthesis and Chemical Biology of Bioactive Molecules2019

    • Author(s)
      Nogawa Toshihiko, Lopez Julius Adam V., Osada Hiroyuki
    • Total Pages
      355
    • Publisher
      Springer
    • ISBN
      9789811362446
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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