Isolation of a Metabolite from the <i>pks</i> Island Provides Insights into Colibactin Biosynthesis and Activity

Abstract

Colibactin is a structurally uncharacterized, genotoxic natural product produced by commensal and pathogenic strains of <i>E. coli</i> that harbor the <i>pks</i> island. A new metabolite has been isolated from a <i>pks</i>⁺ <i>E. coli</i> 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 <i>pks</i>-derived metabolites may exert genotoxicity