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2016 Fiscal Year Final Research Report

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

Research Project

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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
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
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.

Free Research Field

天然物化学

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Published: 2018-03-22  

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