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Production of novel fungal secondary metabolites by epigenetically activating the silent biosynthetic gene clusters.

Research Project

Project/Area Number 23710248
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Living organism molecular science
Research InstitutionTohoku University

Principal Investigator

ASAI Teigo  東北大学, 助教 (60572310)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords天然物 / 二次代謝物 / 糸状菌 / 二次代謝制御 / エピジェネティクス / ヒストン脱 アセチル化酵素 / 酵素阻害剤 / 昆虫寄生菌 / 休眠遺伝子 / 物質生産 / 生物活性物質 / 二次代謝産物 / 天然物化学 / 生理活性物質 / ヒストン脱アセチル化酵素阻害剤 / DNAメチル化酵素阻害剤
Research Abstract

In this study, we found some effective conditions for activating fungal secondary metabolism by using epigenetic modifiers such as HADC and DNA methyltransferase inhibitors. Using the conditions, we successfully isolated structurally diverse novel fungal secondary metabolites from cryptic biosynthetic pathways, showing the utility to enlarge chemical space composed of natural products. In addition, we obtained the evidence that over expression of LaeA, an epigenetic enzyme, in fungi is possible way to enhance their production of secondary metabolites.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (33 results)

All 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (18 results) Remarks (1 results)

  • [Journal Article] Structures and absolute configurations of short-branched fatty acid dimers from an endophytic fungus of Aloe arborescens2013

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

      Tetrahedron Lett

      Volume: (In press) Issue: 26 Pages: 3402-3405

    • DOI

      10.1016/j.tetlet.2013.04.063

    • Related Report
      2012 Annual Research Report 2012 Final 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
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structures and biomimetic synthesis of a Novel α-pyrone polyketide of an endophytic Penicillium sp2013

    • Author(s)
      T, Asai, D. Luo, K. Yamashita, Y. Oshima
    • Journal Title

      Catharanthus roseus, Org. Lett

      Volume: 15 Issue: 5 Pages: 1021-1023

    • DOI

      10.1021/ol303506t

    • Related Report
      2012 Annual Research Report 2012 Final 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
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 糸状菌二次代謝のエピジェネティック制御と天然物探索2013

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

      化学と生物

      Volume: 1 Pages: 13-21

    • NAID

      10031146870

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural Diversity of New C13 -Polyketides Produced by Chaetomium mollipilium Cultivated in the Presence of aNAD+-Dependent Histone DeacetylaseInhibitor2012

    • Author(s)
      T. Asai, S. Morita, N. Shirata, T. Taniguchi, K. Monde, H. Sakurai, T. Ozeki, Y. Oshima
    • Journal Title

      Org. Lett.

      Volume: 14 Issue: 21 Pages: 5456-5459

    • DOI

      10.1021/ol302539s

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclic glycolipids from glandular trichome exudates of Cerastium glomeratum2012

    • Author(s)
      T. Asai, Y. Nakamura, Y. Hirayama, K. Ohyama, Y. Fujimoto
    • Journal Title

      Phytochemistry

      Volume: 82 Pages: 149-157

    • DOI

      10.1016/j.phytochem.2012.07.001

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Highly oxidized ergosterols and isariotin analogs from an entomopathogenic fungus, Gibellula formosana, cultivated in the presence of epigenetic modifying agents2012

    • Author(s)
      T. Asai, Y.-M. Chung, H. Sakurai, T. Ozeki,F.-R. Chang, Y.-C. Wu, K. Yamashita, Y. Oshima
    • Journal Title

      Tetrahedron

      Volume: 68 Issue: 29 Pages: 5817-5823

    • DOI

      10.1016/j.tet.2012.05.020

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epi-α-bisabolol 6-deoxy-β-D-gulopyranoside from the glandular trichome exudate of Brillantaisia owariensis2012

    • Author(s)
      Teigo Asai
    • Journal Title

      Phytochemistry Letters

      Volume: 5 Issue: 2 Pages: 376-378

    • DOI

      10.1016/j.phytol.2012.03.006

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aromatic Polyketide Production in Cordyceps indigotica, an Entomopathogenic Fungus, Induced by Exposure to a Histone Deacetylase Inhibitor2012

    • Author(s)
      T. Asai, T. Yamamoto, Y. Oshima
    • Journal Title

      Org. Lett

      Volume: 14 Pages: 2006-2009

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dihydrobenzofurans as Cannabinoid Receptor Ligands, from Cordyceps annullata, an Entomopathogenic Fungus, Cultivated in the Presence of HDAC Inhibitor2012

    • Author(s)
      Teigo Asai, Dan Luo, Yutaro Obara, Toru Taniguchi, Kenji Monde, Kouwa Yamashita and Yoshiteru Oshima
    • Journal Title

      Tetrahedron Lett

      Volume: 53 Issue: 17 Pages: 2239-2243

    • DOI

      10.1016/j.tetlet.2012.02.088

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tenuipyrone, a Novel Skeletal Polyketide from the Entomopathogenic Fungus, Isaria tenuipes, Cultivated in the Presence of Epigenetic Modifiers2012

    • Author(s)
      T. Asai, Y.-M. Chung, H. Sakurai, T. Ozeki, F.-R. Chang, K. Yamashita, Y. Oshima
    • Journal Title

      Org.Lett.

      Volume: 14 Issue: 2 Pages: 513-515

    • DOI

      10.1021/ol203097b

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aromatic Polyketide Glycosides from an Entomopathogenic Fungus, Cordyceps indigotica2012

    • Author(s)
      Teigo Asai, Takashi Yamamoto, Yu-Ming Chung, Fang-Rong Chang, Yang-Chang Wu, Kouwa Yamashita and Yoshiteru Oshima
    • Journal Title

      Tetrahedron Lett

      Volume: 53 Issue: 3 Pages: 277-280

    • DOI

      10.1016/j.tetlet.2011.10.013

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histone Deacetylase Inhibitor Induced the Production of Three Novel Prenylated Tryptophan Analogs in the Entomopathogenic Fungus, Torrubiella luteorostrata2011

    • Author(s)
      Teigo Asai, Takashi Yamamoto and Yoshiteru Oshima
    • Journal Title

      Tetrahedron Lett

      Volume: 52 Issue: 52 Pages: 7042-7045

    • DOI

      10.1016/j.tetlet.2011.10.020

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] HDAC阻害剤を用いた多様な糸状菌ポリケチド類の創出-Chetomium indicum由来スピロラクトン型新規ポリケチド類の単離構造決定2013

    • Author(s)
      山本崇史,浅井禎吾,谷口透,門出健次,山下幸和,大島吉輝
    • Organizer
      日本薬学会第133回春季年会,横浜
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 糸状菌二次代謝を活性化するNAD+依存型HDAC阻害剤の探索とそれを用いた新規天然物の創出2013

    • Author(s)
      森田峻太郎,浅井禎吾,谷口透,門出健次,櫻井博章,尾関智二,山下幸和,大島吉輝
    • Organizer
      日本薬学会第133回春季年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] HDAC阻害剤を用いた多様な糸状菌ポリケチド類の創出―Chetomium indicum 由来スピロラクトン型新規ポリケチド類の単離構造決定2013

    • Author(s)
      山本崇史
    • Organizer
      日本薬学会第133回春季年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Chaetomium indicumが生産する新規ポリケチドの生合成遺伝子の同定およびHDAC阻害剤を用いた発現制御に関する研究2012

    • Author(s)
      白田直樹,浅井禎吾,大島吉輝
    • Organizer
      第51回日本薬学会東北支部大会
    • Place of Presentation
      青森
    • Year and Date
      2012-10-07
    • Related Report
      2012 Final Research Report
  • [Presentation] NAD+依存型HDAC阻害剤を用いた新規ポリケチドの創出2012

    • Author(s)
      森田峻太郎,浅井禎吾,山下幸和,大島吉輝
    • Organizer
      第51回日本薬学会東北支部大会
    • Place of Presentation
      青森
    • Year and Date
      2012-10-07
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] エピジェネティクスを制御する化学修飾酵素阻害剤を用いた多様な糸状菌ポリケチドの創生2012

    • Author(s)
      浅井禎吾,山本崇史,森田峻太郎,白田直樹,大島吉輝
    • Organizer
      第54回天然有機化合物討論会
    • Place of Presentation
      東京
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] エピジェネティック制御を利用した新規有用物質の探索;昆虫寄生糸状菌Isaria tenuipes由来新規四環式ポリケチドtenuipyroneの単離構造決2012

    • Author(s)
      浅井禎吾,Chung Yu-Ming,櫻井博章,尾関智二,山下幸和,大島吉輝
    • Organizer
      日本薬学会第132回春季年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] HDAC阻害剤を用いた昆虫寄生糸状菌Cordyceps indigoticaおよび植物内生糸状菌Chaetomium indicum由来新規芳香属ポリケチドの創出2012

    • Author(s)
      山本崇史,浅井禎吾,山下幸和,大島吉輝
    • Organizer
      日本薬学会第132回春季年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] エピジェネティック制御を利用した新規有用物質の探索;昆虫寄生糸状菌Cordyceps annullataの生産する新規ジヒドロベンゾフラン類の構造とCB受容体アゴニスト活性2012

    • Author(s)
      羅丹,浅井禎吾,山下幸和,大島吉輝
    • Organizer
      日本薬学会第132回春季年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] Chaetomium indicum が生産する新規ポリケチドの生合成遺伝子の同定およびHDAC阻害剤を用いた発現制御に関する研究2012

    • Author(s)
      白田直樹
    • Organizer
      第51回日本薬学会東北支部大会
    • Place of Presentation
      青森
    • Related Report
      2012 Annual Research Report
  • [Presentation] エピジェネティック制御を利用した新規有用物質の探索; 昆虫寄生糸状菌 Isaria tenuipes 由来新規四環式ポリケチドtenuipyrone の単離構造決定2012

    • Author(s)
      浅井禎吾
    • Organizer
      日本薬学会 第132回年会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Presentation] HDAC阻害剤を利用した昆虫寄生糸状菌Cordyceps annullata由来新規ジヒドロベンゾフラン類の単離構造決定2011

    • Author(s)
      羅丹,浅井禎吾,山下幸和,大島吉輝
    • Organizer
      第50回日本薬学会東北支部大会
    • Place of Presentation
      仙台
    • Year and Date
      2011-10-30
    • Related Report
      2012 Final Research Report
  • [Presentation] エピジェネティックな酵素阻害剤を利用した昆虫寄生糸状菌Cordyceps indigotica由来新規芳香族ポリケチド類の単離構造決定2011

    • Author(s)
      山本崇史,浅井禎吾,山下幸和,大島吉輝
    • Organizer
      第50回日本薬学会東北支部大会
    • Place of Presentation
      仙台
    • Year and Date
      2011-10-30
    • Related Report
      2012 Final Research Report
  • [Presentation] エピジェネティック制御に基づく新規二次代謝物の創出2011

    • Author(s)
      浅井禎吾,山本崇史,Chung Yu-Ming,羅丹,森田峻太郎,白田直樹,山下幸和,大島吉輝
    • Organizer
      第53回天然有機化合物討論会
    • Place of Presentation
      大阪
    • Year and Date
      2011-09-27
    • Related Report
      2012 Final Research Report
  • [Presentation] 低分子阻害剤を用いたエピジェネティック制御に基づく糸状菌由来新規二次代謝物の探索2011

    • Author(s)
      浅井禎吾山本崇史,鐘ユーミン,森田峻太郎,羅丹,山下幸和,大島吉輝
    • Organizer
      第9回次世代を担う有機化学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-05-12
    • Related Report
      2012 Final Research Report
  • [Presentation] 低分子阻害剤を用いたエピジェネティック制御による新規二次代謝物の探索2011

    • Author(s)
      浅井禎吾
    • Organizer
      第9回次世代を担う有機化学シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] 第53回天然有機化合物討論会2011

    • Author(s)
      浅井禎吾
    • Organizer
      エピジェネティック制御に基づく新規二次代謝物の創出
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report
  • [Presentation] AMECS 112011

    • Author(s)
      Teigo Asai
    • Organizer
      Fungal Secondary Metabolite Production by Chemical Epigenetic Manipulation of Silent Gene Clusters
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

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

    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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