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Characterization of genotoxins, colibactin, facilitating inflammation-induced colorectal cancer

Research Project

Project/Area Number 26560450
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Chemical biology
Research InstitutionUniversity of Shizuoka

Principal Investigator

Watanabe Kenji  静岡県立大学, 薬学部, 教授 (50360938)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords大腸がん / 生合成 / 遺伝性毒素 / 大腸菌 / 腸内細菌層 / 診断マーカー / 脂質 / ペプチド / コリバクチン / 天然物 / ケミカルバイオロジー / シンセティックバイオロジー / 腸内細菌 / 天然物化学
Outline of Final Research Achievements

Colibactins are natural products produced by select commensal, extraintestinal, and probiotic Escherichia coli. Strains of E. coli possessing clb gene cluster induce DNA damage in eukaryotic cells and are thought to promote colorectal cancer formation. However, the chemical structure of colibactin as a final product has been covered yet. In this study, we tried to isolate and characterize colibactin and biosynthetic precursor of colibactin from mutated E. coli Nissle 1917, which is colibactin producing strain. Spectroscopic analysis of chemical structures of precursors by using NMR, myristol-CoA connected with peptide has been isolated from deficiency of clbP (peptidase as a proposed function) mutant of E. coli Nissle 1917. Based on the biosynthetic gene cluster responsible for the formation of colibactin, these chemical structures were partially anticipated due to coding for the hybrid polyketide synthase-nonribosomal peptide synthetase in clb.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (11 results)

All 2017 2015 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (3 results)

  • [Int'l Joint Research] University of California, Los Angeles(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Biochemical and structural basis for controlling chemical modularity in fungal polyketide biosynthesis.2015

    • Author(s)
      Winter, J. M., Cascio, D., Dietrich, D., Sato, M., Watanabe, K., Sawaya, M., Vederas, J. C., Tang, Y.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 31 Pages: 9885-9893

    • DOI

      10.1021/jacs.5b04520

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tandem prenyltransferases catalyze isoprenoid elongation and complexity generation in biosynthesis of quinolone alkaloids.2015

    • Author(s)
      Zou, Y., Zhan, Z., Li, D., Tang, M., Watanabe, K., Tang, Y.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 15 Pages: 4980-4983

    • DOI

      10.1021/jacs.5b03022

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Genetic indoctrination of Escherichia coli for finding genotoxins “colibactin” facilitating inflammation-induced colorectal cancer2017

    • Author(s)
      Kenji Watanabe
    • Organizer
      U.S.-Japan Cooperative Medical Sciences Program (USJCMSP) Cancer Panel Meeting
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2017-02-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Biosynthesis of a Cancer–Inducing Compound in Escherichia coli2015

    • Author(s)
      Masao Oohashi, Yuzuka Sasa, Noriyasu Ishikawa, Hiroshi Noguchi and Kenji Watanabe
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Honolulu, Hawaii, USA.
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大腸がん原因物質colibactinの化学構造解明2015

    • Author(s)
      大橋雅生、渡辺賢二
    • Organizer
      天然物談話会
    • Place of Presentation
      宮城県岩沼市
    • Year and Date
      2015-07-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 大腸がん原因物質コリバクチンの生合成機構の解明2015

    • Author(s)
      佐々侑寿香、石川格靖、小山ふみ、福冨愛実、野口博司、渡辺賢二
    • Organizer
      日本農芸化学会2015年度大会(岡山)
    • Place of Presentation
      岡山大学
    • Year and Date
      2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 大腸がん原因物質コリバクチンの生合成機構の解明2015

    • Author(s)
      佐々侑寿香、石川格靖、小山ふみ、福冨愛実、野口博司、渡辺賢二
    • Organizer
      日本薬学会第135年会(神戸)
    • Place of Presentation
      兵庫医療大学
    • Year and Date
      2015-03-26
    • Related Report
      2014 Research-status Report
  • [Remarks] WATANABE RESEARCH GROUP

    • URL

      http://sweb.u-shizuoka-ken.ac.jp/~kenji55-lab/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 発表予定

    • URL

      http://www015.upp.so-net.ne.jp/kenji55-lab/index.html

    • Related Report
      2015 Research-status Report
  • [Remarks] 大腸がんの原因物質の解明に大きく前進!

    • URL

      http://www.pharm.or.jp/nenkai/135highlight4_abstract.pdf

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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