Exploring the Diversity and Specificity of Secondary Biosynthetic Potential in Rhodococcus

The actinomycete genus <i>Rhodococcus</i> is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in <i>Rhodococcus</i>. The diversity and specificity of its secondary metabolism offer valuable insights for exploring natural products, yet remain understudied. In the present study, we analyzed the distribution patterns of biosynthetic gene clusters (BGCs) in the most comprehensive <i>Rhodococcus</i> genome data to date. The results show that 86.5% of the gene cluster families (GCFs) are only distributed in a specific phylogenomic-clade of <i>Rhodococcus</i>, with the most predominant types of gene clusters being NRPS and ribosomally synthesized and post-translationally modified peptides (RiPPs). In-depth mining of RiPP gene clusters revealed that <i>Rhodococcus</i> encodes many clade-specific novel RiPPs, with thirteen core peptides showing antibacterial potential. High-throughput elicitor screening (HiTES) and non-targeted metabolomics revealed that a marine-derived <i>Rhodococcus</i> strain produces a large number of new aurachin-like compounds when exposed to specific elicitors. The present study highlights the diversity and specificity of secondary biosynthetic potential in <i>Rhodococcus</i>, and provides valuable information for the targeted exploration of novel natural products from <i>Rhodococcus</i>, especially for phylogenomic-clade-specific metabolites.