Divergent biosynthesis yields a cytotoxic aminomalonate-containing precolibactin

Colibactin represents 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 that uniquely incorporates the highly sought genotoxicity-associated aminomalonate building block in its unprecedented macrocyclic structure. This work provides new insights into the biosynthetic logic and mode of action of this colorectal cancer-linked microbial chemical.