• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Study on biosynthetic machinery of type II polyketide synthase

Research Project

Project/Area Number 18H02144
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38040:Bioorganic chemistry-related
Research InstitutionThe University of Tokyo

Principal Investigator

Katsuyama Yohei  東京大学, 大学院農学生命科学研究科(農学部), 准教授 (50646437)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Keywordsポリケタイド / 生合成 / 放線菌 / 二次代謝 / 酵素 / polyketide / biosynthesis / enzyme / actinobacteria / secondary metabolite / enzymes / ポリエン / ポリケタイド合成酵素 / 芳香族化合物 / polyketide synthase / Streptomyces / natural products
Outline of Final Research Achievements

We focused on the polyketides produced by actinomycetes and analyzed their biosynthesis. Twenty gene disruption strains were generated based on the yorpyrazone producer strain, and their metabolism was analyzed. The results showed that the biosynthetic intermediate of yoropyrazone is a griseusin derivative. Furthermore, we succeeded in reconstituting part of the biosynthesis of griseusin derivatives in vitro. We also analyzed a part of the biosynthetic pathway of fogacin in vitro. We also worked on the X-ray crystallographic analysis of a particularly interesting enzyme among them. We also analyzed how polyketide synthase regulates protein-protein interactions and efficiently produces secondary metabolites, and elucidated some of the mechanisms.

Academic Significance and Societal Importance of the Research Achievements

放線菌の生産する芳香族ポリケタイドは抗がん剤であるドキソルビシンのように有用な生物活性を持つものが数多く存在する。これらの生合成機構を深く理解することで、これらの化合物の生合成経路の人為的な改変を実現し、より生物活性の良い化合物や安定性の高い化合物の創出につながる。今回、生合成機構が未知であった芳香族ポリケタイドの生合成機構が複数明らかになった。また、これらの化合物の生合成にはタンパク質タンパク質間の相互作用メカニズムを理解することが大事であるが、それに関してもいくつかの重要な知見が得られた。本研究を継続し、これらの理解がさらに進めば新たな医薬品化合物候補の創出につながると期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (13 results)

All 2022 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Remarks (1 results)

  • [Int'l Joint Research] UCSD(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Structural basis for selectivity in a highly reducing type II polyketide synthase.2020

    • Author(s)
      Danyao Du, Yohei Katsuyama, Masanobu Horiuchi, Shinya Fushinobu, Aochiu Chen, Tony D. Davis, Michael D. Burkart, Yasuo Ohnishi
    • Journal Title

      Nature Chemical Biology

      Volume: 未定 Issue: 7 Pages: 776-782

    • DOI

      10.1038/s41589-020-0530-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Involvement of β‐Alkylation Machinery and Two Sets of Ketosynthase‐Chain‐Length Factors in the Biosynthesis of Fogacin Polyketides in Actinoplanes missouriensis2019

    • Author(s)
      Sato Kei、Katsuyama Yohei、Yokota Kousuke、Awakawa Takayoshi、Tezuka Takeaki、Ohnishi Yasuo
    • Journal Title

      ChemBioChem

      Volume: 20 Issue: 8 Pages: 1039-1050

    • DOI

      10.1002/cbic.201800640

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 芳香族ポリケタイドyoropyrazone のスピロ環形成機構のin vitro 解析2022

    • Author(s)
      清藤 鈴奈、勝山 陽平、大西 康夫
    • Organizer
      日本農芸化学会2022年度 京都大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 放線菌の持つ窒素酸化物を利用した二次代謝の多様性2022

    • Author(s)
      勝山 陽平
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 2つのII型PKSとFAS間におけるACPのクロストークに関するin vitro解析2020

    • Author(s)
      ○堀内 真展、杜 丹ヤオ、勝山 陽平、Burkart, Michael D.、大西 康夫
    • Organizer
      日本農芸化学会2020年度 福岡大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 放線菌の持つ二次代謝経路の探索と機能解析2019

    • Author(s)
      勝山 陽平
    • Organizer
      第18回微生物研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 高還元型II型PKS由来KS-CLFヘテロダイマー及びACP-KS-CLF三者複合体のX線結晶構造解析2019

    • Author(s)
      杜 丹ヤオ、勝山 陽平、伏信 進矢、Chen Aochiu、Davis Tony D、Burkart Michael、大西 康夫
    • Organizer
      日本農芸化学会2019年度 東京大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Streptomyces sp. IFM11307 由来芳香族ポリケタイド yoropyrazone 生合成に関する研究2018

    • Author(s)
      藤田 夏澄, 勝山 陽平, 當銘 一文, 石橋 正己, 大西 康夫
    • Organizer
      第33回 (2018年度) 日本放線菌学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Reconstitution of a Type II Polyketide Synthase Catalyzing Polyene Formation2018

    • Author(s)
      Danyao Du, Yohei Katsuyama, Kazuo Shin-ya, Yasuo Ohnishi
    • Organizer
      3rd European Conference on Natural Products
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 放線菌の持つ多様な二次代謝産物の生合成機構2018

    • Author(s)
      勝山 陽平
    • Organizer
      第五回天然物化学研究会 東京農業大学世田谷キャンパス
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 放線菌のもつ多様な二次代謝産物生合成機構の解析2018

    • Author(s)
      勝山 陽平
    • Organizer
      第3回関東支部例会 東京大学農学部弥生講堂一条ホール日本農芸化学会奨励賞受賞講演
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Remarks] 醗酵学研究室

    • URL

      http://park.itc.u-tokyo.ac.jp/hakko/index.php

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi