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Activation of fungal silent secondary metabolite gene clusters using the CRISPR/Cas9 system.

Research Project

Project/Area Number 18K05420
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38020:Applied microbiology-related
Research InstitutionThe University of Tokyo (2021-2022)
Institute of Physical and Chemical Research (2018-2020)

Principal Investigator

YUN CHOONGSOO  東京大学, 大学院農学生命科学研究科(農学部), 特任助教 (40432801)

Co-Investigator(Kenkyū-buntansha) 本山 高幸  国立研究開発法人理化学研究所, 環境資源科学研究センター, 専任研究員 (70291094)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords菌類 / 二次代謝 / ゲノム編集 / 糸状菌 / CRISPR/Cas9
Outline of Final Research Achievements

The recent large-scale sequencing of fungal genomes has shown that fungi are richer in secondary metabolism-related genes than once believed. However, the majority of these genes are silent under laboratory culture conditions. Silent gene clusters represent a promising resource for the development of new therapeutic agents. Unfortunately, the characterization of secondary metabolites produced by these clusters is frequently hampered owing to our inability to express these gene clusters. To overcome this bottleneck, here I conducted the research project for activation of fungal silent secondary metabolite biosynthesis gene clusters using the powerful genome editing technology, CRISPR/dCas9-transcriptional activation factor system and I succeed that activating the tenuazonic acid production in P. oryzae using this system.

Academic Significance and Societal Importance of the Research Achievements

昨今、世界的に抗生物質が効かない多剤耐性菌の増加や新しい感染症の拡散が問題視されているなか、新規抗生物質や治療剤のリード化合物になり得る糸状菌二次代謝産物発掘は大いに注目されている。この観点から休眠二次代謝遺伝子群の活性化及び代謝産物の獲得は社会に大きく貢献できると考えられる。本研究で提案したCRIPSR/dCas9システムを応用した休眠二次代謝遺伝子群の活性化方法は新規有用代謝産物獲得に適用できる可能性を示した。まだ細部的なシステムの改良などが必要であるが今後の研究で解決できると考えている。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Unique features of the ketosynthase domain in a nonribosomal peptide synthetase?polyketide synthase hybrid enzyme, tenuazonic acid synthetase 12020

    • Author(s)
      Yun Choong-Soo、Nishimoto Kazuki、Motoyama Takayuki、Shimizu Takeshi、Hino Tomoya、Dohmae Naoshi、Nagano Shingo、Osada Hiroyuki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 33 Pages: 11602-11612

    • DOI

      10.1074/jbc.ra120.013105

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新しいタイプの二次代謝酵素TAS1のホモログを活用した新規生理活性天然化合物の発掘2020

    • Author(s)
      本山高幸、野川俊彦、清水猛、川谷誠、二村友史、尹忠銖、長田裕之
    • Organizer
      令和元年度日本農芸学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ケトシンターゼドメインによるかび毒テヌアゾン酸の環状骨格形成メカニズム2019

    • Author(s)
      尹忠銖、西本一希、本山高幸、日野智也、永野真吾、長田裕之
    • Organizer
      糸状菌分子生物学研究会19回コンファレンス
    • Related Report
      2019 Research-status Report
  • [Presentation] イネいもち病菌における二次代謝活性化2019

    • Author(s)
      本山高幸、野川俊彦、石井友彬、尹忠銖、長田裕之
    • Organizer
      第61回天然有機化合物討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] 環化反応を触媒する新規ケトシンターゼドメインのX線結晶構造解析2019

    • Author(s)
      尹 忠銖、西本 一希、本山 高幸、日野 智也、永野 真吾、長田 裕之
    • Organizer
      平成31年度日本農芸学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Timing of tenuazonic acid production at the infection plant pathogenic fungi.2018

    • Author(s)
      Choong-Soo YUN, Takeshi Kashiwa, Takayuki Motoyama, Hiroyuki Osada
    • Organizer
      1st Japanese-German Symposium: Biosynthesis and Function of Natural Products
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulatory mechanism of mycotoxin tenuazonic acid biosynthesis in Pyricularia oryzae2018

    • Author(s)
      Choong-Soo YUN, Takayuki Motoyama, Hiroyuki Osada
    • Organizer
      3rd European Conference on Natural Products
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] カビ毒テヌアゾン酸の環状骨格を形成するTAS1 KSドメインのX線結晶構造解析2018

    • Author(s)
      西本 一希、尹 忠銖、本山 高幸、長田 裕之、日野 智也、永野 真吾
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Crystallization analysis of ketosynthase domain that responsible for cyclic skeleton formation of tenuazonic acid2018

    • Author(s)
      Choong-Soo Yun, Kazuki Nishimoto, Takayuki Motoyama, Tomoya Hino, Shingo Nagano, Hiroyuki Osada
    • Organizer
      The 9th Japan-Korea Chemial Biology Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2024-01-30  

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