Characterization of an aryl polyene biosynthetic gene cluster superfamily widespread among Gram-negative bacteria

The ClusterFinder algorithm was developed in our group to scan sequenced bacterial genomes for biosynthetic gene clusters (BGCs), irrespective of the compound class they are predicted to produce. Among the multitude of BGCs of unknown function identified by ClusterFinder, we focused on two large families containing hundreds of ~20kb BGCs that contain genes encoding unusual ketosynthase and adenylation domains.

We took a genetic approach to characterize the clusters from the uropathogenic Escherichia coli CFT073 and the squid symbiont Vibrio fischeri ES114 as representatives for each family. Heterologous expression and deletion analyses showed that both clusters encode for the production of cell-wall-associated yellow pigmentation and that compound production is under specific regulatory control.

Purification and structural analysis identified the products of these two gene clusters as aryl polyenes (APEs). Their structure is similar to the pigments flexirubin and xanthomonadin, members of a distantly related third family. Together, the APE superfamily constitutes the largest family of BGCs in the sequence database (containing >1000 members). The widespread phylogenetic distribution of APEs in human (Escherichia, Bacteroides, Campylobacter, …), animal (Vibrio, Flexibacter) or plant (Xanthomonas, Pseudomonas) symbionts and/or pathogens suggests an important function for APEs in a host-associated bacterial lifestyle.