Figure 7.

Model of colibactin biosynthesis. The NRPS-PKS assembly line is posttranslationally matured with a 4′-phosphopantetheine (PP) arm on the carrier proteins by the ClbA PP transferase. The active assembly line synthesizes precolibactin that is translocated in the periplasm by the ClbM efflux pump. The prodrug is cleaved by the ClbP peptidase to generate the cleavage product (black) and active mature colibactin (red). Self-damage to the producing bacterium DNA by active colibactin is prevented by the periplasmic maturation and by the cytoplasmic ClbS resistance protein.