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Biosynthetic research on cryptic gene activation

Research Project

Project/Area Number 17K19233
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Agricultural chemistry and related fields
Research InstitutionKyoto University

Principal Investigator

Kakeya Hideaki  京都大学, 薬学研究科, 教授 (00270596)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords天然物化学 / ケミカルバイオロジー / 複合培養 / クリプティック遺伝子 / 生合成 / 放線菌 / 希少放線菌
Outline of Final Research Achievements

The common biosynthetic gene cluster for both antifungal 5-alkyl-1,2,3,4-tetrahydroquinolines (5aTHQs) and antimicrobial streptoaminals (STAMS) produced by the combined-culture of Streptomyces sp. HEK616 and Tsukamurella sp. TP-B0596 were identified. The gene cluster contained nine genes including a unique type II PKS system.
Meanwhile, an unstable intermediate of saccharothriolides production, presaccharothriolide C2 produced by the rare actinomycete Saccharothrix sp. A1506 was discovered, and precursor-directed in situ synthesis (PDSS) method was established.

Academic Significance and Societal Importance of the Research Achievements

本研究課題の成果は、微生物の潜在的物質生産能力の覚醒や微生物代謝産物中の不安定生合成中間体の実証に関して大きなブレークスルーになる可能性を秘めている。特に、クリプティック遺伝子の活性化を起点としたモノづくり研究に関する研究成果は、創薬リード化合物を指向した新規二次代謝産物の探索・同定研究およびケミカルスペースの拡充研究などに貢献可能であり、学術的にも社会的にも意義は大きい。

Report

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

    (25 results)

All 2019 2018 2017 Other

All Int'l Joint Research (6 results) Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results) Book (2 results) Remarks (2 results)

  • [Int'l Joint Research] トロント大学(カナダ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] スイス連邦工科大学(スイス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] プリンストン大学(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ライプニッツ天然有機化合物研究所(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] プリンストン大学(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] スイス連邦工科大学(スイス)

    • Related Report
      2017 Research-status Report
  • [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] Enhancement of saccharothriolide production and discovery of a new metabolite, saccharothriolide C2, by combined-culture of Saccharothrix sp. and Tsukamurella pulmonis2019

    • Author(s)
      Yulu Jiang, Shan Lu, Go Hirai, Taira Kato, Hiroyasu Onaka, Hideaki Kakeya
    • Journal Title

      Tetrahedron Lett.

      Volume: 60 Issue: 15 Pages: 1072-1074

    • DOI

      10.1016/j.tetlet.2019.03.034

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Natural products-inspired chemical biology toward developmentof new antibiotics2018

    • Author(s)
      Hideaki Kakeya
    • Journal Title

      Jpn. J. Antibiot.

      Volume: 71 Pages: 181-191

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of presaccharothriolide X, a retro-Michael product of saccharothriolide B, from the rare actinomycete Saccharothrix sp. A15062018

    • Author(s)
      Shan Lu, Shinichi Nishimura, Kei Takenaka, Masashi Ito, Taira Kato, Hideaki Kakeya
    • Journal Title

      Org. Lett.

      Volume: 20 Issue: 15 Pages: 4406-4410

    • DOI

      10.1021/acs.orglett.8b01535

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 生体膜を標的にする天然有機化合物:天然物による厳密な脂質認識とそれに基づく表現型2018

    • Author(s)
      西村慎一, 掛谷秀昭, 松森信明
    • Journal Title

      化学と生物

      Volume: 56 Pages: 678-685

    • NAID

      130007709540

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery Scienceに魅せられて:天然物創薬ケミカルバイオロジーの最前線2018

    • Author(s)
      掛谷秀昭
    • Journal Title

      化学と生物

      Volume: 56 Pages: 210-216

    • NAID

      130007601848

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Precursor-directed in situ synthesis of saccharothriolides G and H by the actinomycete Saccharothrix sp.2017

    • Author(s)
      Shan Lu, Shinich Nishimura, Masashi Ito, Taira Kato, Hideaki Kakeya
    • Journal Title

      J. Antibiot.

      Volume: 70 Issue: 5 Pages: 718-720

    • DOI

      10.1038/ja.2016.153

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 化学コミュニケーションが織りなす生命科学2019

    • Author(s)
      掛谷秀昭
    • Organizer
      日本化学会第99春季年会(2019)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Development of cryptic antifungal 5aTHQs targting cell membranesignaling2019

    • Author(s)
      Hideaki Kakeya
    • Organizer
      Asian Chemical Biology Initiative (ACBI) 2019 Yangon Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 医薬品シード分子の多様性創出と細胞内標的探索・同定2018

    • Author(s)
      掛谷秀昭
    • Organizer
      京大テックフォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 天然物創薬ケミカルバイオロジー~放線菌に魅せられて~2018

    • Author(s)
      掛谷秀昭
    • Organizer
      2018年度(第33回)日本放線菌学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 天然物創薬ケミカルバイオロジーの醍醐味2018

    • Author(s)
      掛谷秀昭
    • Organizer
      第53回天然物化学談話会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Microbial metabolites targeting microenvironment: a cell membranesigaling modulator and a hypoxia-response modulator2018

    • Author(s)
      Hideaki Kakeya
    • Organizer
      The 9th Japan-Koreachemical biology symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Expansion of chemical space in saccharothriolides: Precursor-directed in situ synthesis (PDSS) in a rare actinomycete Saccharothrix sp.2018

    • Author(s)
      Shan Lu, Shinichi Nishimura, Masashi Ito, Taira Kato, Hideaki Kakeya
    • Organizer
      Natural Product Discovey & Development in the Genomic Era (Natural Products 2018)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 「シンポジウム:これからの天然物サイエンス」―ケミカルスペース拡充戦略:微生物複合培養法及びPDSS (Precurso-Directed in situ Synthesis)法―2018

    • Author(s)
      掛谷秀昭
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] ケミカルバイオロジー化合物集2018

    • Author(s)
      日本におけるケミカルバイオロジーの新展開第189委員会
    • Total Pages
      304
    • Publisher
      オーム社
    • ISBN
      9784274507090
    • Related Report
      2018 Annual Research Report
  • [Book] 1. 薬の基礎知識 & 2. 創薬の世界, Newton 別冊 「くすりの科学知識:くすりのしくみと、奥深き創薬の世界」2017

    • Author(s)
      掛谷秀昭(監修)
    • Total Pages
      144
    • Publisher
      ニュートンプレス社
    • ISBN
      9784315520835
    • Related Report
      2017 Research-status Report
  • [Remarks] 京都大学大学院薬学研究科 医薬創成情報科学専攻 システムケモセラピー(制御分子学)分野

    • URL

      http://www.pharm.kyoto-u.ac.jp/sc-molsci/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都大学大学院薬学研究科 医薬創成情報科学専攻 システムケモセラピー(制御分子学)分野

    • URL

      http://www.pharm.kyoto-u.ac.jp/sc-molsci/

    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2022-02-21  

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