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the mode of action in the combined-culture methods that induce potential secondary metabolism

Research Project

Project/Area Number 18H02120
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38020:Applied microbiology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Hiroyasu Onaka  東京大学, 大学院農学生命科学研究科(農学部), 特任教授 (80315829)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords共培養 / 天然物スクリーニング / 抗生物質生産 / 放線菌 / ミコール酸 / 微生物間相互作用 / 二次代謝産物 / 複合培養 / 生合成 / 微生物相互作用 / 二次代謝 / ミコール酸含有細菌
Outline of Final Research Achievements

Actinomycetes are known to conduct a wide variety of secondary metabolisms. Many secondary metabolites have been discovered from actinomycetes and have been used as pharmaceutical drugs. However, genome analysis has revealed that only a few secondary metabolites have been discovered in actinomycetes, and that many potential secondary metabolites have not yet been discovered.
The discovery of such potential secondary metabolites is expected to lead to the development of new drugs. Therefore, we have established a "combined-culture" as a method to activate potential secondary metabolisms, and have already discovered over 35 new secondary metabolites. This method was inspired by the soil environment in which actinomycetes generally live, and it activates the potential secondary metabolism of actinomycetes by co-culture of mycolic acid-containing bacteria (MACB) and actinomycetes. In this study, we investigated the mode of action in the combined-culture.

Academic Significance and Societal Importance of the Research Achievements

天然物は医薬品の供給源として重要である。特に、昨今のコロナウイルスを初めとした多様な感染症被害は依然として人類の脅威であるため、新たな医薬品の開発は重要な研究テーマの一つである。複合培養法は微生物由来天然物の探索に有用な技術である。多様な天然物を生産することが知られている放線菌とミコール酸含有細菌を共培養することにより、従来の純粋培養では生産しなかった様々な天然物を放線菌が生産するようになる。今回の研究では、複合培養の作用機構解明を進めた。また、複合培養を用いた天然物探索も進め、新たに12種類の新規天然物の発見に成功した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (13 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Longicatenamides A-D, two diastereomeric pairs of cyclic hexapeptides produced by combined-culture of Streptomyces sp. KUSC_F05 and Tsukamurella pulmonis TP-B05962021

    • Author(s)
      Jiang, Y., Matsumoto, T., Kuranaga, T., Lu, S., Wang, W., Onaka, H., Kakeya, H.
    • Journal Title

      J. Antibiot.

      Volume: - Issue: 5 Pages: 307-316

    • DOI

      10.1038/s41429-020-00400-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amycolapeptins A and B, cyclic nonadepsipeptides produced by combined-culture of Amicolatopsis sp. and Tsukamurella pulmonis2021

    • Author(s)
      Pan, C., Kuranaga, T., Cao, X., Suzuki, T., Dohmae, N., Shinzato, N., Onaka, H., Kakeya, H.
    • Journal Title

      J. Org. Chem.

      Volume: 86 Issue: 2 Pages: 1843-1849

    • DOI

      10.1021/acs.joc.0c02660

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Chemical Interactions of Cryptic Actinomycete Metabolite 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines through Aggregate Formation2019

    • Author(s)
      Sugiyama Ryosuke、Nakatani Takahiro、Nishimura Shinichi、Takenaka Kei、Ozaki Taro、Asamizu Shumpei、Onaka Hiroyasu、Kakeya Hideaki
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 58 Issue: 38 Pages: 13486-13491

    • DOI

      10.1002/anie.201905970

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of the common biosynthetic gene cluster for both antimicrobial streptoaminals and antifungal 5-alkyl-1,2,3,4-tetrahydroquinolines2019

    • Author(s)
      Ozaki Taro、Sugiyama Ryosuke、Shimomura Morito、Nishimura Shinichi、Asamizu Shumpei、Katsuyama Yohei、Kakeya Hideaki、Onaka Hiroyasu
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 17 Issue: 9 Pages: 2370-2378

    • DOI

      10.1039/c8ob02846j

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of silent biosynthetic pathways and discovery of novel secondary metabolites in actinomycetes by co-culture with mycolic acid-containing bacteria2018

    • Author(s)
      Hoshino Shotaro、Onaka Hiroyasu、Abe Ikuro
    • Journal Title

      Journal of Industrial Microbiology & Biotechnology

      Volume: 46 Issue: 3-4 Pages: 363-374

    • DOI

      10.1007/s10295-018-2100-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catenulobactins A and B, Heterocyclic Peptides from Culturing Catenuloplanes sp. with a Mycolic Acid-Containing Bacterium2018

    • Author(s)
      Hoshino Shotaro、Ozeki Masahiro、Awakawa Takayoshi、Morita Hiroyuki、Onaka Hiroyasu、Abe Ikuro
    • Journal Title

      Journal of Natural Products

      Volume: 81 Issue: 9 Pages: 2106-2110

    • DOI

      10.1021/acs.jnatprod.8b00261

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] RNA-seq解析に基づいた複合培養における二次代謝活性化機構の解析2021

    • Author(s)
      木田 優士、浅水 俊平、尾仲 宏康
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 複合培養におけるStreptomyces coelicolorのRED生産遅延に関与するTetR型転写制御因子の解析2021

    • Author(s)
      LEI YUKUN、浅水 俊平、石塚 匠、栁澤 昌臣、大野 豊、佐藤 勝也、尾仲 宏康
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 放線菌と土壌細菌との相互作用2021

    • Author(s)
      浅水 俊平、尾仲 宏康
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Introduction2020

    • Author(s)
      H. Onaka
    • Organizer
      The 5th A3 Foresight Symposium on “Chemical & Synthetic Biology of Natural Products”
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 複合培養における赤色色素生産非応答性変異株の解析2019

    • Author(s)
      石塚 匠、浅水 俊平、栁澤 昌臣、佐藤 勝也、尾仲 宏康
    • Organizer
      2019年度日本農芸化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Combined-culture: Potential secondary metabolism is promoted by co-culture with mycolic acid containing bacteria2019

    • Author(s)
      Hiroyasu Onaka
    • Organizer
      2nd China-Japan Joint Symposium on Natural Product Biosynthesis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Combined-culture: potential secondary metabolism is promoted by co-culture with mycolic acid containing bacteria2018

    • Author(s)
      Hiroyasu Onaka
    • Organizer
      The Japanese-German Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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