The geranyl-modified tryptophan residue is crucial for ComXRO-E-2 pheromone biological activity

The ComX pheromone is an isoprenoidal oligopeptide containing a modified tryptophan residue, which stimulates natural genetic competence in gram-positive bacteria, Bacillus. We have reported the structure of the ComXRO-E-2 pheromone, which is produced by the RO-E-2 strain of Bacillus subtilis. ComXRO-E-2 analogs with substituted amino acids and isoprenoid modified tryptophan residues (e.g., prenyl, geranyl, and farnesyl), were synthesized and examined for biological activity. These results indicate that Phe-Trp∗(Ger)-NH2 is the minimum pharmacophore of the ComXRO-E-2 pheromone. Furthermore, the length of the isoprenoid moiety (i.e., modification style), and the presence of double bonds, are crucial for biological activity. The modification style of the ComX pheromone is more important than the peptide sequence with respect to biological activity.

Graphical abstractResearch of structure–activity relationships on ComXRO-E-2 pheromone, a quorum sensing pheromone, indicates Phe-Trp∗(Ger)-NH2 is a minimal pharmacore.Figure optionsDownload full-size imageDownload as PowerPoint slide