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Chemical biology on cryptic genes activation

Research Project

Project/Area Number 15K14721
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Bioorganic chemistry
Research InstitutionKyoto University

Principal Investigator

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

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsケミカルバイオロジー / 天然物化学 / 複合培養 / 生物有機化学 / 生合成 / 抗真菌剤 / 抗生物質 / クリプティック遺伝子
Outline of Final Research Achievements

During a high-throughput screening for identifying cell membrane modulators, eight novel 5-alkyl-1,2,3,4-tetrahydroquinolines (5aTHQs) bearing different side chains have been isolated from a combined-culture of Streptomyces sp. HEK616 and Tsukamurella pulmonis TP-B0596. The chemical structures including the absolute configuration were determined by spectroscopic analysis and total synthesis. Moreover, stable isotopic feeding experiments with sodium [1-13C]-acetate and [1,2-13C]-acetate in the combined-culture revealed that 5aTHQs is biosynthesized via a polyketide pathway. In addition, there novel streptoaminals were identified by an extensive mass spectrometry analysis against the combined-culture broth. These results suggest that the microbial combined-culture has a big potential for a range of chemical scaffolds.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (19 results)

All 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Peer Reviewed: 5 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 8 results) Remarks (2 results)

  • [Int'l Joint Research] University of Florida/University of San Diego(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 創薬ケミカルバイオロジー:自然に学ぶ薬づくり2017

    • Author(s)
      掛谷秀昭
    • Journal Title

      「くすりをつくる研究者の仕事―薬のタネ探しから私たちに届くまで」

      Volume: - Pages: 63-82

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Discovery and Total Synthesis of Streptoaminals: Antimicrobial [5,5]-Spirohemiaminals from  the Combined-Culture of Streptomyces nigrescens and Tsukamurella pulmonis.2016

    • Author(s)
      Sugiyama R, Nishimura S, Ozaki T, Asamizu S, Onaka H, Kakeya H.
    • Journal Title

      Angew Chem Int Ed Engl.

      Volume: 55(35) Issue: 35 Pages: 10278-10282

    • DOI

      10.1002/anie.201604126

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Natural products-prompted chemical biology: Phenotypic screening and a new platform for target identification2016

    • Author(s)
      Kakeya, H.
    • Journal Title

      Nat. Prod. Rep.

      Volume: 33 Issue: 5 Pages: 648-654

    • DOI

      10.1039/c5np00120j

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 感染症の脅威と闘う―ヒトマイクロバイオームと特殊培養デバイスの活用2016

    • Author(s)
      都築健悟, 掛谷秀昭
    • Journal Title

      化学

      Volume: 71 Pages: 70-71

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 5-Alkyl-1,2,3,4-tetrahydroquinolines, New Membrane-Interacting Lipophilic Metabolites Produced by Combined Culture of Streptomyces nigrescens and Tsukamurella pulmonis.2015

    • Author(s)
      Sugiyama R, Nishimura S, Ozaki T, Asamizu S, Onaka H, Kakeya H.
    • Journal Title

      Org Lett.

      Volume: 印刷中 Issue: 8 Pages: 1918-1921

    • DOI

      10.1021/acs.orglett.5b00607

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 創薬ケミカルバイオロジー: シード分子開発と分子プロファイリング2015

    • Author(s)
      掛谷秀昭
    • Journal Title

      生体の科学

      Volume: 66 Pages: 119-125

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 生体膜微小環境への挑戦:膜ステロールに作用する海洋天然物セオネラミド2015

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

      CSJカレントレビュー19号(日本化学会編)「生物活性分子のケミカルバイオロジー」

      Volume: 19 Pages: 102-108

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 新しい抗真菌薬シード開発と適応拡大戦略」―抗真菌薬開発のためのケミカルバイオロジー研究方略:シード分子開発とメカニズム解析2017

    • Author(s)
      掛谷秀昭
    • Organizer
      技術情報協会セミナー
    • Place of Presentation
      東京
    • Year and Date
      2017-08-02
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] アカデミア創薬における表現型スクリーニングと次世代天然物化学2017

    • Author(s)
      掛谷秀昭
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都
    • Year and Date
      2017-03-18
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 創薬ケミカルバイオロジー研究方略:表現型スクリーニングとシード分子開発2017

    • Author(s)
      掛谷秀昭
    • Organizer
      ビッグデータ駆動型創薬システム研究拠点・第3回シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 微生物の複合培養で得られる5aTHQとstreptoaminalの構造と構造2016

    • Author(s)
      西村慎一, 杉山龍介, 仲谷崇宏, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭
    • Organizer
      第21回天然薬物の開発と応用シンポジウム
    • Place of Presentation
      千葉
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Microbial metabolites-prompted chemical biology: Phenotypic screening and a new platform for target identification2016

    • Author(s)
      Kakeya, H
    • Organizer
      The Fifth Symposium of RIKEN-Max Planck Joint Research Center for System Chemical Biology
    • Place of Presentation
      Germany
    • Year and Date
      2016-04-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 脂質結合性天然物の活用―放線菌複合培養液より見出した新規アルカロイド群に関する研究2016

    • Author(s)
      杉山龍介, 西村慎一, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 5-Alkyl-1,2,3,4-tetrahydroquinolines (5aTHQs), new membrane-interacting lipophilic metabolites, produced by combined-culture of Streptomyces nigrescens and Tsukamurella pulmonis2015

    • Author(s)
      Sugiyama, R., Nishimura, S., Ozaki, T., Asamizu, S., Onaka, H., Kakeya, H.
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2015 (PACIFICHEM 2015)
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      2015-12-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Natural products-prompted chemical biology; Phenotypic screening and target identification2015

    • Author(s)
      Kakeya, H.
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2015 (PACIFICHEM 2015)
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] シンポジウム「創薬の将来」. 創薬ケミカルバイオロジー:シード分子開発と分子プロファイリング2015

    • Author(s)
      掛谷秀昭
    • Organizer
      第63回日本化学療法学会総会
    • Place of Presentation
      東京
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] 京都大学大学院薬学研究科 システムケモセラピー(制御分子学)分野・研究室ホームページ

    • URL

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

    • Related Report
      2016 Annual Research Report
  • [Remarks] 京都大学大学院薬学研究科システムケモセラピー(制御分子学)分野研究室ホームページ

    • URL

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

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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