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微生物基因毒素大肠杆菌素的生物合成与生物活性

Biosynthesis and bioactivities of microbial genotoxin colibactins.

作者信息

Tang Jian-Wei, Liu Xin, Ye Wei, Li Zhong-Rui, Qian Pei-Yuan

机构信息

Department of Ocean Science, Hong Kong Branch of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), The Hong Kong University of Science and Technology, Kowloon, Hong Kong, China.

Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou 511458, China.

出版信息

Nat Prod Rep. 2022 May 26;39(5):991-1014. doi: 10.1039/d1np00050k.

DOI:10.1039/d1np00050k
PMID:35288725
Abstract

Covering: up to 2021Colibactin(s), a group of secondary metabolites produced by the island ( cluster) of , shows genotoxicity relevant to colorectal cancer and thus significantly affects human health. Over the last 15 years, substantial efforts have been exerted to reveal the molecular structure of colibactin, but progress is slow owing to its instability, low titer, and elusive and complex biosynthesis logic. Fortunately, benefiting from the discovery of the prodrug mechanism, over 40 precursors of colibactin have been reported. Some key biosynthesis genes located on the island have also been characterised. Using an integrated bioinformatics, metabolomics, and chemical synthesis approach, researchers have recently characterised the structure and possible biosynthesis processes of colibactin, thereby providing new insights into the unique biosynthesis logic and the underlying mechanism of the biological activity of colibactin. Early developments in the study of colibactin have been summarised in several previous reviews covering various study periods, whereas the two most recent reviews have focused primarily on the chemical synthesis of colibactin. The present review aims to provide an update on the biosynthesis and bioactivities of colibactin.

摘要

涵盖时间

截至2021年

大肠杆菌素是由大肠杆菌的基因岛(簇)产生的一组次级代谢产物,具有与结直肠癌相关的基因毒性,因此对人类健康有重大影响。在过去15年里,人们为揭示大肠杆菌素的分子结构付出了巨大努力,但由于其不稳定性、低滴度以及难以捉摸且复杂的生物合成逻辑,进展缓慢。幸运的是,得益于前体药物机制的发现,已报道了40多种大肠杆菌素的前体。位于基因岛上的一些关键生物合成基因也已得到表征。研究人员最近采用综合生物信息学、代谢组学和化学合成方法,确定了大肠杆菌素的结构和可能的生物合成过程,从而为大肠杆菌素独特的生物合成逻辑及其生物活性的潜在机制提供了新见解。在之前几篇涵盖不同研究时期的综述中总结了大肠杆菌素研究的早期进展,而最近的两篇综述主要集中在大肠杆菌素的化学合成上。本综述旨在提供有关大肠杆菌素生物合成和生物活性的最新情况。

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1
Biosynthesis and bioactivities of microbial genotoxin colibactins.微生物基因毒素大肠杆菌素的生物合成与生物活性
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Current understandings of colibactin regulation.当前对大肠杆菌素调控的理解。
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