《生命科学》 2020, 32(12): 1288-1295

基因毒素colibactin的生物合成和功能研究进展

陈艳飞^1,2 , 王　亨^1,2 , 王培莉^1,2 , 朱国强^1,2 , 孟　霞^1,2,*

¹扬州大学兽医学院，扬州 225009 ²江苏省动物重要疫病与人兽共患病防控协同创新中心，扬州 225009

摘　要：

Colibactin 是细菌产生的一种具有遗传毒性的次级代谢产物，于2006 年首次被发现，由于产量小、不稳定，至今无法从细菌中直接分离纯化。该文重点总结了colibactin 的生物合成过程、结构、生物学功能和检测等相关的研究进展。Colibactin 由杂合的非核糖体肽合成酶- 聚酮合酶(NRPS-PKS) 装配线合成，该装配线由54 kb 的pks 基因岛编码，基因岛上19 个编码基因全部参与了合成过程。化学合成法阐明了colibactin 的结构是一种含有两个能与DNA 反应的亲电环丙烷残基的异源二聚体。Colibactin 可诱导真核细胞DNA 链间交联，导致双链断裂(DSB) 和染色体不稳定，产colibactin 细菌的存在与结肠癌、败血症、新生儿脑膜炎和尿路感染等疾病的发生有关。

通讯作者：孟　霞 , Email:mengxia_1@126.com

Research progress on the biosynthesis and function of genotoxin colibactin

CHEN Yan-Fei^1,2 , WANG Heng^1,2 , WANG Pei-Li^1,2 , ZHU Guo-Qiang^1,2 , MENG Xia^1,2,*

¹College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China ²Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China

Abstract:

Colibactin is a genotoxic secondary metabolite produced by bacteria. It was first discovered in 2006, but because it is unstable and produced in small quantity, it has not been isolated by now. In this review, we summarize advances in biosynthesis process, structure, biological effects and detection of colibactin. Colibactin is synthesized by a hybrid non-ribosomal peptide synthetase-polyketide synthase (NRPS-PKS) assembly line, which is encoded by the 54-kilobase genomic island pks. All 19 genes in the island are involved in the synthesis process. The structure of colibactin was identified as a heterodimer containing two DNA-reactive electrophilic cyclopropane residues by chemical synthesis method. Colibactin has been shown to form interstrand cross-links of DNA in eukaryotic cells, resulting in double-strand break (DSB) and chromosome instability. The existence of colibactin-producing bacteria is associated with the occurrence of diseases such as colon cancer, neonatal meningitis and urinary tract infection.

Communication Author：MENG Xia , Email:mengxia_1@126.com