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Secondary metabolite Screening by combined-culture

Research Project

Project/Area Number 25292046
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Applied microbiology
Research InstitutionThe University of Tokyo

Principal Investigator

Onaka Hiroyasu  東京大学, 農学生命科学研究科, 教授 (80315829)

Co-Investigator(Kenkyū-buntansha) 宮本 憲二  慶應義塾大学, 理工学部, 准教授 (60360111)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords複合培養 / 生合成 / 放線菌 / 抗生物質 / 共培養 / ミコール酸 / 遺伝子発現 / 二次代謝 / 応用微生物 / バイオテクノロジー / 醗酵 / シグナル伝達 / 抗生物質生産
Outline of Final Research Achievements

Streptomyces have the potential to produce more than 30 secondary metabolites; however, the expression of most metabolite biosynthetic gene clusters is cryptic or silent. Indeed, the expression of these genes is conditional and dependent on culture conditions. To activate such gene clusters, many methods have been developed. Combined-culture which is developed by our group is a coculture method to activate secondary metabolism in Streptomyces. The activator strains are mycolic acid-containing bacteria, and about 90% of Streptomyces species show changes in secondary metabolism in combined-culture compared with pure culture. In this project, we revealed that pigment induction was mediated by cell-to-cell physical contact. In addition, we applied combined-culture to new secondary metabolite screening, and then new secondary metabolites (5-aTHQ, chojyalactone, arcyriaflavin E, niizalactam) are discovered. Thus, combined-culture may have applications in natural product-based drug discovery.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (37 results)

All 2016 2015 2014 2013 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 7 results) Presentation (26 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results) Book (1 results) Remarks (2 results)

  • [Journal Article] 複合培養による放線菌抗生物質生産の覚醒2016

    • Author(s)
      尾仲宏康
    • Journal Title

      バイオインダストリー

      Volume: 3 Pages: 4-10

    • 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] Insights into the Biosynthesis of Dehydroalanines in Goadsporin2016

    • Author(s)
      Taro Ozaki, Yukari Kurokawa, Shohei Hayashi, Naoya Oku, Shumpei Asamizu, Yasuhiro Igarashi, Hiroyasu Onaka
    • Journal Title

      Chembiochem

      Volume: 17 Issue: 3 Pages: 218-223

    • DOI

      10.1002/cbic.201500541

    • NAID

      120006313535

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Niizalactams A-C, multicyclic macrolactams isolated from combined culture of Streptomyces with mycolic acid-containing bacterium2015

    • Author(s)
      S. Hoshino, M. Okada, T. Wakimoto, H. Zhang, F. Hayashi, H. Onaka, I. Abe
    • Journal Title

      J. Nat. Prod.

      Volume: 78 Issue: 12 Pages: 3011-3017

    • DOI

      10.1021/acs.jnatprod.5b00804

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Chojalactones A-C, Cytotoxic Butanolides Isolated from Streptomyces sp. Cultivated with Mycolic Acid Containing Bacterium.2015

    • Author(s)
      Hoshino S, Wakimoto T, Onaka H, Abe I.
    • Journal Title

      Org Lett.

      Volume: 印刷中 Issue: 6 Pages: 1501-1504

    • DOI

      10.1021/acs.orglett.5b00385

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mycolic acid-containing bacteria activate heterologous secondary metabolite expression in Streptomyces lividans.2015

    • Author(s)
      Onaka H, Ozaki T, Mori Y, Izawa M, Hayashi S, Asamizu S.
    • Journal Title

      J Antibiot (Tokyo)

      Volume: 印刷中 Issue: 9 Pages: 594-597

    • DOI

      10.1038/ja.2015.31

    • NAID

      120005844159

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Arcyriaflavin E, a new cytotoxic indolocarbazole alkaloid isolated by combined-culture of mycolic acid-containing bacteria and Streptomyces cinnamoneus NBRC 13823.2014

    • Author(s)
      S. Hoshino, L. Zhang, T. Awakawa, T. Wakimoto, H. Onaka, I. Abe
    • Journal Title

      J. Antibiot.

      Volume: 67 Issue: 5 Pages: 1-3

    • DOI

      10.1038/ja.2014.147

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Streptomyces davawensis JCM 4913 において新規亜硝酸生合成経路を用いて生合成される二次代謝産物の同定2016

    • Author(s)
      萩原亮太、勝山陽平、菅井佳宣、尾仲宏康、大西康夫
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] RNA-seqによるミコール酸含有細菌に対するStreptomyces coelicolor A3(2)の応答解析2016

    • Author(s)
      佐々木槇子、浅水俊平、尾崎太郎、宮本憲二、尾仲宏康
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      コンベンションセンター(北海道・札幌市)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] Combined-culture: the new method for secondary metabolism activation in actinomycetes2015

    • Author(s)
      Hiroyasu Onaka
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      ホノルル(米国)
    • Year and Date
      2015-12-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 微生物が有する休眠抗生物質生産系の活性化2015

    • Author(s)
      尾仲宏康
    • Organizer
      第38回分子生物学会年会・第88回生化学会大会合同大会
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 共生にもとづく微生物潜在機能の発掘2015

    • Author(s)
      尾仲宏康
    • Organizer
      日本農芸化学会大会2015年度大会シンポジウム
    • Place of Presentation
      岡山大学
    • Year and Date
      2015-03-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 複合培養における放線菌二次代謝の誘導要因の探索2015

    • Author(s)
      浅水 俊平、尾崎 太郎、佐藤 勝也、尾仲 宏康
    • Organizer
      日本農芸化学会大会2015年度一般講演
    • Place of Presentation
      岡山大学
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 複合培養を用いたStreptomyces属放線菌由来新規二次代謝産物の探索2015

    • Author(s)
      星野翔太郎、張驪駻、淡川孝義、脇本敏幸、尾仲宏康、阿部郁朗
    • Organizer
      日本薬学会 第135年会
    • Place of Presentation
      岡山大学
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Secondary metabolites induction by mycolic acid-containing bacteria in Streptomyces2015

    • Author(s)
      Shumpei Asamizu, Taro Ozaki, Hiroyasu Onaka
    • Organizer
      Natural Product Discovery and Development in the Post Genomic Era
    • Place of Presentation
      SanDiego(アメリカ)
    • Year and Date
      2015-01-11 – 2015-01-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] 5-Alkyl-1,2,3,4-tetrahydroquinolines, membrane-interacting lipophilic metabolites, found in combined-culture of Streptomyces sp. HEK616 and Tsukamurella pulmonis2015

    • Author(s)
      Ryosuke Sugiyama, Shinichi Nishimura, Taro Ozaki, Hiroyasu Onaka and Hideaki Kakeya
    • Organizer
      Natural Product Discovery and Development in the Post Genomic Era
    • Place of Presentation
      SanDiego(アメリカ)
    • Year and Date
      2015-01-11 – 2015-01-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] ミコール酸含有微生物との複合培養を用いたStreptomyces属放線菌由来新規生物活性物質の探索2014

    • Author(s)
      星野翔太郎、張驪駻、淡川孝義、脇本敏幸、尾仲宏康、阿部郁朗
    • Organizer
      東京大学生物生産工学研究センターシンポジウム
    • Place of Presentation
      東京大学弥生講堂
    • Year and Date
      2014-12-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] 複合培養法:共培養を利用した放線菌からの天然物探索2014

    • Author(s)
      尾仲宏康
    • Organizer
      第7回北陸合同バイオシンポジウムin 越中八尾
    • Place of Presentation
      富山市
    • Year and Date
      2014-11-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] ミコール酸含有微生物との複合培養による Streptomyces属放線菌由来新規生物活性物質の探索2014

    • Author(s)
      星野翔太郎、張驪駻、淡川孝義、脇本敏幸、尾仲宏康、阿部郁朗
    • Organizer
      第20回天然薬物の開発と応用シンポジウム
    • Place of Presentation
      東京大学弥生講堂
    • Year and Date
      2014-11-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 複合培養法:細胞間接触による二次代謝活性化を利用した天然物探索2014

    • Author(s)
      尾仲宏康
    • Organizer
      第20回天然薬物の開発と応用シンポジウム
    • Place of Presentation
      東京大学弥生講堂
    • Year and Date
      2014-11-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ミコール酸含有細菌との複合培養を用いた、Streptomyces属放線菌由来新規生物活性物質の探索2014

    • Author(s)
      星野翔太郎、張驪駻、淡川孝義、脇本敏幸、尾仲宏康、阿部郁朗
    • Organizer
      第4回 CSJ化学フェスタ2014
    • Place of Presentation
      江戸川区
    • Year and Date
      2014-10-14 – 2014-10-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Combined induction: a fermentation method for heterologous secondary metabolite production in Streptomyces2014

    • Author(s)
      Hiroyasu Onaka, Shumpei Asamizu, Taro Ozaki
    • Organizer
      17th International symposium on biology of actinomycetes
    • Place of Presentation
      Kusadasi, Turkey
    • Year and Date
      2014-10-08 – 2014-10-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] ミコール酸含有微生物との複合培養を用いた、放線菌Streptomyces属由来新規生物活性物質の探索2014

    • Author(s)
      星野翔太郎、張驪駻、淡川孝義、脇本敏幸、尾仲宏康、阿部郁朗
    • Organizer
      日本生薬学会第61回年会
    • Place of Presentation
      福岡大学
    • Year and Date
      2014-09-13 – 2014-09-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] ミコール酸含有微生物Tsukamurella pulmonisとの複合培養による、放線菌Streptomyces属由来新規生物活性物質の探索2014

    • Author(s)
      星野翔太郎、張驪駻、淡川孝義、脇本敏幸、尾仲宏康、阿部郁朗
    • Organizer
      第29回日本放線菌学会大会
    • Place of Presentation
      つくば市
    • Year and Date
      2014-06-19 – 2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 複合培養を利用した新規テトラヒドロキノリン類の単離とその生合成に関する研究2014

    • Author(s)
      尾崎太郎、杉山龍介、西村慎一、浅水俊平、掛谷秀昭、尾仲宏康
    • Organizer
      第29回日本放線菌学会大会
    • Place of Presentation
      つくば市
    • Year and Date
      2014-06-19 – 2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 死細胞は放線菌の二次代謝を複合培養において誘導しない2014

    • Author(s)
      浅水俊平、尾崎太郎、尾仲宏康
    • Organizer
      第29回日本放線菌学会大会
    • Place of Presentation
      つくば市
    • Year and Date
      2014-06-19 – 2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 異属細菌による放線菌二次代謝産物の誘導2014

    • Author(s)
      浅水俊平、尾仲宏康
    • Organizer
      日本農芸化学会関東支部例会
    • Place of Presentation
      東京大学弥生講堂
    • Year and Date
      2014-05-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 複合培養に応答するgodAプロモーター領域の解析2013

    • Author(s)
      浅水俊平, 小野拓人, 林昌平, 尾﨑太郎, 尾仲宏康
    • Organizer
      2013年度(第28回)日本放線菌学会大会
    • Place of Presentation
      メルパルクホール(広島県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Combined induction: a fermentation method for heterologous secondary metabolite production in Streptomyces2013

    • Author(s)
      Hiroyasu Onaka
    • Organizer
      12. 1st European Conference on Natural Products: Research and Application
    • Place of Presentation
      Frunkfurt (Germany)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Combined induction: effective fermentation procedure for heterologous secondary metabolite production in actinomycetes

    • Author(s)
      Hiroyasu Onaka, Yukiko Mori, Masumi Izawa, Shohei Hayashi
    • Organizer
      12th International Symposium on the Genetics of Industrial Microorganisms
    • Place of Presentation
      Cancun (Mexico)
    • Related Report
      2013 Annual Research Report
  • [Presentation] "Combined culture" and "combined induction": Activation of sleeping enzymatic genes involved in the secondary metabolism of actinomycetes

    • Author(s)
      Hiroyasu Onaka
    • Organizer
      17th German-Japanese Workshop on Enzyme Technology
    • Place of Presentation
      Hamburg (Germany)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 放線菌における潜在的抗生物質生産能力の覚醒技術

    • Author(s)
      尾仲宏康
    • Organizer
      発酵と代謝研究会シンポジウム「放線菌によるヒト・動物医薬と農薬への貢献-探索と選抜、機能解析から新規開拓へ-」
    • Place of Presentation
      東京大学(東京都)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 微生物同士の接触刺激による抗生物質生産機

    • Author(s)
      尾仲宏康
    • Organizer
      第21回農芸化学Frontiersシンポジウム
    • Place of Presentation
      デュープレックスホテル(茨城県)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] 複合培養による放線菌抗生物質生産の覚醒2016

    • Author(s)
      尾仲宏康
    • Total Pages
      10
    • Publisher
      CMC出版
    • Related Report
      2015 Annual Research Report
  • [Remarks] 東京大学微生物潜在機能探索寄付講座ホームページ

    • URL

      http://microbial-potential.bt.a.u-tokyo.ac.jp/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 部生物潜在機能探索寄付講座ホームページ

    • URL

      http://microbial-potential.bt.a.u-tokyo.ac.jp/

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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