Isolation of a Metabolite from the pks Island Provides Insights into Colibactin Biosynthesis and Activity

• DOI: 10.1021/acs.orglett.5b00432
• Publication Date: 2015-03-10T10:26:48Z
• Authors: Carolyn A. Brothe...; Matthew Wilson; Gary Byrd; Emily P. Balskus
• Keywords: 0303 health sciences; 03 medical and health sciences; Molecular Structure; Polyketides; Escherichia coli; Humans; Peptides; DNA Damage; 3. Good health

Colibactin is a structurally uncharacterized, genotoxic natural product produced by commensal and pathogenic strains of E. coli that harbor the pks island. A new metabolite has been isolated from a pks(+) E. coli mutant missing an essential biosynthetic enzyme. The unusual azaspiro[2.4] bicyclic ring system of this molecule provides new insights into colibactin biosynthesis and suggests a mechanism through which colibactin and other pks-derived metabolites may exert genotoxicity.