Escherichia coli-Derived γ-Lactams and Structurally Related Metabolites Are Produced at the Intersection of Colibactin and Fatty Acid Biosynthesis

Autor:	Tayah Turocy, Chung Sub Kim, Jason M. Crawford, Emilee E. Shine, Gyuri Moon
Rok vydání:	2021
Předmět:	chemistry.chemical_classification Metabolite Organic Chemistry Locus (genetics) Peptide Nuclear magnetic resonance spectroscopy medicine.disease_cause Biochemistry chemistry.chemical_compound chemistry In vivo Colibactin medicine Physical and Theoretical Chemistry Escherichia coli Genotoxicity
Zdroj:	Organic Letters. 23:6895-6899
ISSN:	1523-7052 1523-7060
DOI:	10.1021/acs.orglett.1c02461
Popis:	Colibactin is a genotoxic hybrid polyketide-nonribosomal peptide that drives colorectal cancer initiation. While clinical data suggest colibactin genotoxicity in vivo is largely caused by the major DNA-cross-linking metabolite, the colibactin locus produces a diverse collection of metabolites with mostly unknown biological activities. Here, we describe 10 new colibactin pathway metabolites (1-10) that are dependent on its α-aminomalonyl-carrier protein. The most abundant metabolites, 1 and 2, were isolated and structurally characterized mainly by nuclear magnetic resonance spectroscopy to be γ-lactam derivatives, and the remaining related structures were inferred via shared biosynthetic logic. Our proposed formation of 1-10, which is supported by stereochemical analysis, invokes cross-talk between colibactin and fatty acid biosynthesis, illuminating further the complexity of this diversity-oriented pathway.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::353db4dc169052b8906f62aef1e22be5 https://doi.org/10.1021/acs.orglett.1c02461 Zobrazit plný text záznamu