10 - Posttranslational Isoprenylation of Tryptophan Residues in Bacillus subtilis

Abstract

Bacillus subtilis and related bacilli produce a posttranslationally modified oligopeptide termed “ComX pheromone” that stimulates natural genetic competence controlled by quorum sensing. ComX pheromones are modified with either a geranyl or farnesyl group on a conserved tryptophan residue at the 3-position of its indole ring, resulting in the formation of a tricyclic structure that includes a newly formed five-membered ring similar to proline. ComX pheromone is the first example of not only isoprenoidal modification of tryptophan residues in living organisms but also posttranslational isoprenylation in prokaryotes. As the geranylation of peptides—including monoterpene metabolites—is unusual in prokaryotes, posttranslational geranylation is unprecedented in nature. The modification of ComX pheromones with isoprenoid plays a more essential role for establishing genetic competence than the amino acid sequence. Based on the initial discovery of posttranslational isoprenylation of cysteine in pheromones secreted by eukaryotic microorganisms, which was later revealed to be a widespread phenomenon, it is speculated that posttranslational isoprenylation of tryptophan will also be recognized as a universal modification and will respond to important biological function in the near future.