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Discovery of Novel Natural Products from Fungi by Epigenetic Expression of Secondary Metabolite Biosynthetic Genes

Research Project

Project/Area Number 25293022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Natural medicines
Research InstitutionTohoku University

Principal Investigator

Oshima Yoshiteru  東北大学, 薬学研究科(研究院), 教授 (00111302)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords糸状菌 / 未利用生合成遺伝子 / 天然物創出 / ケミカルエピジェネティクス / 二次代謝物 / エピジェネティクス / 構造多様性 / 天然物 / 未利用遺伝子 / エピジェネシス / 化学変換 / ケミカルスペース
Outline of Final Research Achievements

Fungi living in plants or arthropods are attractive resources for our natural product exploration using chemical epigenetic method. After the isolation of various fungi from medicinal plants and arthropods, mainly insects and spiders, the chemical epigenetic method was applied to the fungi and found Graphiopsis chlorocephala (Paeonia lactiflora) and Mycosphaerella sp. (Aloe arborescens) were found to enhance the accumulation of their secondary metabolites, from which structurally diverse novel benzophenones and short branched fatty acid dimers were isolated.
Structurally diverse chaetophenols were previously isolated from Chaetomium fungi as novel natural products by using chemical epigenetic method, and simple aromatic compound was biosynthesized by a NR-PKS gene as a common intermediate of chaetophenols. Overexpression of the gene in Aspergillus oryzae and artificial chemical transformation of the aromatic compound generated various novel pseudo-natural products.

Report

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

    (21 results)

All 2015 2014 2013 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (10 results) (of which Invited: 2 results) Remarks (3 results)

  • [Journal Article] Use of a Biosynthetic Intermediate to Explore the Chemical Diversity of Pseudo-natural Fungal Polyketides2015

    • Author(s)
      T. Asai*, K. Tsukada, S. Ise, N. Shirata, M. Hashimoto, I. Fujii, K. Gomi, K. Nakagawara, E. N. Kodama, Y, Oshima
    • Journal Title

      Nature Chem.

      Volume: 7 Issue: 9 Pages: 737-743

    • DOI

      10.1038/nchem.2308

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Benzophenones from an Endophytic Fungus, Graphiopsis chlorocephala, from Paeonia lactiflora Cultivated in the Presence of an NAD+-Dependent HDAC Inhibitor2013

    • Author(s)
      T. Asai, S. Otsuki, H. Sakurai, K.Yamashita, T. Ozeki, Y. Oshima
    • Journal Title

      Org.Lett

      Volume: 15 Issue: 8 Pages: 2058-2061

    • DOI

      10.1021/ol400781b

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structures and absolute configurations of short-branched fatty acid dimers from an endophytic fungus of Aloe arborescens2013

    • Author(s)
      Teigo Asai, Sae Otsuki, Tohru Taniguchi, Kenji Monde, Kouwa Yamashita, Hiroaki Sakurai, Tomoji Ozeki and Yoshiteru Oshima
    • Journal Title

      Tetrahedron Lett.

      Volume: 54 Pages: 3402-3405

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An epigenetic modifier enhances the production of anti-diabetic and anti-inflammatory sesquiterpenoids from Aspergillus sydowii2013

    • Author(s)
      Y. M. Chung, C. K. Wei, D. W. Chuang, M. E. Shazly, C. T. Hsieh, T. Asai, Y. Oshima, T. J. Hsieh, T. L. Hwang, Y. C. Wu, F. R. Chang
    • Journal Title

      Bioorg. Med. Chem

      Volume: 21 Issue: 13 Pages: 3866-3872

    • DOI

      10.1016/j.bmc.2013.04.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structurally Diverse Chaetophenol Productions Induced by Chemically Mediated Epigenetic Manipulation of Fungal Gene Expression2013

    • Author(s)
      T. Asai, T. Yamamoto, N. Shirata, T. Taniguchi, K. Monde, I. Fujii, K. Gomi, Y. Oshima
    • Journal Title

      Org. Lett.

      Volume: 15 Issue: 13 Pages: 3346-3349

    • DOI

      10.1021/ol401386w

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suberoylanilide Hydroxamic Acid, a Histone Deacetylase Inhibitor, Induces the Production of Anti-inflammatory Cyclodepsipeptides from Beauveria felina2013

    • Author(s)
      Y. M. Chung, M. E. Shazly, D. W. Chuang, T. L. Hwang, T. Asai, Y. Oshima, M. L. Ashour, Y. C. Wu, F. R. Chang
    • Journal Title

      J. Nat. Prod.

      Volume: 76 Issue: 7 Pages: 1260-1266

    • DOI

      10.1021/np400143j

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structures of Spiroindicumides A and B, Unprecedented Carbon Skeletal Spirolactones, and Determination of the Absolute Configuration by Vibrational Circular Dichroism Exciton Approach.2013

    • Author(s)
      Teigo Asai, Tohru Taniguchi, Takashi Yamamoto, Kenji Monde, Yoshiteru Oshima
    • Journal Title

      Org. Lett.

      Volume: 15 Issue: 17 Pages: 4320-4323

    • DOI

      10.1021/ol401741z

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ケミカルエピジェネティクスによる未利用生合成遺伝子の活用と多様な天然物の創出2013

    • Author(s)
      浅井禎吾, 大島吉輝
    • Journal Title

      ファルマシア

      Volume: 50 Pages: 112-116

    • NAID

      130005143935

    • Related Report
      2013 Annual Research Report
  • [Presentation] 天然物化学の再興を目指して:ケミカルエピジェネティクスと天然物の創出2015

    • Author(s)
      大島吉輝
    • Organizer
      創薬懇話会2015 in 徳島
    • Place of Presentation
      鳴門
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 糸状菌の休眠遺伝子をいかにして“ものとり”に活用するか:二次代謝誘導と天然物探索2014

    • Author(s)
      浅井禎吾
    • 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
    • Year and Date
      2014-11-05 – 2014-11-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 身近な生物に内生する多様な糸状菌を資源とした新規天然物探索2014

    • Author(s)
      布木純
    • 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
    • Year and Date
      2014-11-05 – 2014-11-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] Chaetophenol類の生合成中間体を活用したポリケタイド分子多様性の拡大2014

    • Author(s)
      塚田健人
    • 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
    • Year and Date
      2014-11-05 – 2014-11-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] Chaetomium indicumの休眠遺伝子を活用した新規二次代謝物の獲得2014

    • Author(s)
      伊藤史織
    • 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
    • Year and Date
      2014-11-05 – 2014-11-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 糸状菌NR-PKSが生合成する芳香族ポリケタイドを起点とした2014

    • Author(s)
      浅井禎吾
    • Organizer
      第56回天然有機化合物討論会
    • Place of Presentation
      高知
    • Year and Date
      2014-10-15 – 2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Chaetophenol 類の生合成とエピジェネティック制御に関する研究2014

    • Author(s)
      浅井禎吾,白田直樹,森田峻太郎,塚田健人,藤井勲,五味勝也,大島吉輝
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] ツツジ科植物内生糸状菌を資源とした新規天然物の探索2014

    • Author(s)
      大槻 紗恵,浅井禎吾,山下幸和,大島吉輝
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] エピジェネティックな二次代謝活性化法を利用するイチイ内生糸状菌からの新規生物活性物質の探索2014

    • Author(s)
      布木純,浅井禎吾,山下幸和,河治久実,児玉栄一,大島吉輝
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 糸状菌の単純芳香族ポリケタイドから複雑な二量化ポリケタイドの創生2014

    • Author(s)
      塚田健人,浅井禎吾,白田直樹,藤井勲,五味勝也,大島吉輝
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Remarks] 東北大学大学院薬学研究科 医薬資源化学分野

    • URL

      http://www.pharm.tohoku.ac.jp/~shigen/lab/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 東北大学大学院 医薬資源化学分野

    • URL

      http://www.pharm.tohoku.ac.jp/~shigen/lab/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東北大学大学院薬学研究科 医薬資源化学分野

    • URL

      http://www.pharm.tohoku.ac.jp/~shigen/lab/index.html

    • Related Report
      2013 Annual Research Report

URL: 

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

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