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

Abstract

ABSTRACT 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. IMPORTANCE Genome mining studies have revealed the remarkable combinatorial diversity of ribosomally synthesized and post-translationally modified peptides (RiPPs) in marine bacteria, including prochlorosins. However, mining strategies also prove valuable in investigating the genomic landscape of associated genes within biosynthetic gene cluster (BGC) specific to targeted RiPPs of interest. Our study contributes to the enrichment of knowledge regarding prochlorosin diversity. It offers insights into potential mechanisms involved in their biosynthesis and modification, such as hyper-modification, which may give rise to active lantibiotics. Additionally, our study uncovers putative novel promiscuous post-translational enzymes, thereby expanding the chemical space explored within the Synechococcus genus. Moreover, this research extends the applications of mining techniques beyond the discovery of new RiPP-like clusters, allowing for a deeper understanding of genomics and diversity. Furthermore, it holds the potential to reveal previously unknown functions within the intriguing RiPP families, particularly in the case of prochlorosins.