title: Critical Intermediates Reveal New Biosynthetic Events in the Enigmatic Colibactin Pathway.
abstract: Colibactin is a potent genotoxin that induces DNA double-strand breaks; it is produced by Escherichia coli strains harboring a pks+ island. However, the structure of this compound remains elusive. Here, using transformation-associated recombination (TAR) cloning to perform heterologous expression, we took advantage of the significantly increased yield of colibactin pathway-related compounds to determine and isolate a series of vital (pre)colibactin intermediates. The chemical structures of compounds 8, 10 and 11 were identified by NMR and MS(n) analyses. The new 1H-pyrrolo[3,4-c]pyridine-3,6(2H,5H)-dione- and thiazole-containing compound 10 provides new insights regarding the biosynthetic pathway to (pre)colibactin and establishes foundations for future investigation of the intriguing (pre)colibactin structures and its modes of action.
authors.affiliation: Division of Life Science and Environmental Science Programs, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong (China).
authors.forename: Zhong-Rui
authors.initials: ZR
authors.lastname: Li
authors.affiliation: Division of Life Science and Environmental Science Programs, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong (China).
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Life Science and Environmental Science Programs, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong (China).
authors.forename: Jennifer Y H
authors.initials: JY
authors.lastname: Lai
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresource and Eco-Environmental, Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Science, Shenzhen University, Shenzhen 518060 (P. R. China).
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Tang
authors.affiliation: Zhejiang Provincial Engineering Technology Research Center of Marine, Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, 1st Haidanan Road, Lincheng, Zhoushan 316022 (P. R. China).
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Division of Life Science and Environmental Science Programs, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong (China).
authors.forename: Liang
authors.initials: L
authors.lastname: Lu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, 88 South University Avenue, Yangzhou, Jiangsu 225009 (P. R. China).
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Food Science and Engineering, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632 (P. R. China).
authors.forename: Xiyang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresource and Eco-Environmental, Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Science, Shenzhen University, Shenzhen 518060 (P. R. China).
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Division of Life Science and Environmental Science Programs, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong (China). boqianpy@ust.hk.
authors.forename: Pei-Yuan
authors.initials: PY
authors.lastname: Qian
mesh_terms: D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010455:Peptides; D061065:Polyketides; C569566:colibactin
keywords: Escherichia coli; colibactin; heterologous expression; precolibactin; prodrug mechanism