Uncovering the diversity and distribution of biosynthetic gene clusters of prochlorosins and other putative RiPPs in marine Synechococcus strains

Picocyanobacteria can synthesize a distinctive class of lanthipeptides referred to as prochlorosins. They are classified within the Nif11 family and are subject to post-translational modifications by a solitary promiscuous enzyme from the ProcM group. Their biological function is unknown but highly speculated upon. In this study, we conducted a comprehensive genome mining investigation of the Synechococcus and Prochlorococcus genomes to elucidate the genomic landscape associated with the biosynthetic gene clusters (BGCs) harboring prochlorosin genes. Our mining study led to a substantial expansion of the known prochlorosin repertoire identified in 15 picocyanobacterial genomes. We also identified a range of tailoring enzymes and gene families proximal to the procA/syncA genes. The recombination-related proteins we detected were of particular interest, as they may have a critical role in generating the diversity observed within this peptide family. Interestingly, we identified novel LAP/YcaO BGCs in Synechococcus that had not been previously described. These BGCs hold the potential to generate prochlorosins with secondary modifications and introduce new putative azol(in)e-containing ribosomally synthesized and post-translationally modified peptides precursors. Our investigation offers an in-depth analysis of the vast prochlorosin family.