title: Divergent biosynthesis yields a cytotoxic aminomalonate-containing precolibactin.
abstract: Colibactin is an as-yet-uncharacterized genotoxic secondary metabolite produced by human gut bacteria. Here we report the biosynthetic discovery of two new precolibactin molecules from Escherichia coli, including precolibactin-886, which uniquely incorporates the highly sought genotoxicity-associated aminomalonate building block into its unprecedented macrocyclic structure. This work provides new insights into the biosynthetic logic and mode of action of this colorectal-cancer-linked microbial chemical.
authors.affiliation: Division of Life Science and Environmental Science Programs, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Zhong-Rui
authors.initials: ZR
authors.lastname: Li
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: High-field NMR Research Center, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.
authors.forename: Jin-Ping
authors.identifier: 0000-0001-5800-3624
authors.initials: JP
authors.lastname: Gu
authors.affiliation: Division of Life Science and Environmental Science Programs, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Jennifer Y H
authors.initials: JY
authors.lastname: Lai
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Brendan M
authors.identifier: 0000-0002-7034-8374
authors.initials: BM
authors.lastname: Duggan
authors.affiliation: Division of Life Science and Environmental Science Programs, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Wei-Peng
authors.initials: WP
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Zhi-Long
authors.initials: ZL
authors.lastname: Li
authors.affiliation: Division of Life Science and Environmental Science Programs, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Rong-Biao
authors.initials: RB
authors.lastname: Tong
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresource &Ecoenvironmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: High-field NMR Research Center, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Lin
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California, USA.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Moore
authors.affiliation: Division of Life Science and Environmental Science Programs, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Pei-Yuan
authors.initials: PY
authors.lastname: Qian
mesh_terms: D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008314:Malonates / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008314:Malonates; D010455:Peptides; D061065:Polyketides; C569566:colibactin; C019249:aminomalonic acid