Genome mining for ribosomally synthesised and post-translationally modified peptides (RiPPs) reveals undiscovered bioactive potentials of actinobacteria.

One of the most diverse groups of bioactive bacterial metabolites is the ribosomally synthesised and post-translationally modified peptides (RiPPs) with different bioactivities. The process of genome mining has made it possible to predict the presence of such clusters among the huge genomic data available today. Despite the great potential of actinobacteria in producing natural products and the myriad of completely sequenced genomes available, a comprehensive genome mining of these bacteria for RiPPs is lacking. Here, a collection of 629 complete actinobacterial genomes were analysed to explore their RiPP biosynthesis potential. Using BAGEL3 genome mining tool, the presence of 477 RiPP biosynthesis gene clusters (BGCs) was shown, including all known classes of bacterial RiPPs. RiPP-encoding potential was shown to be widespread among different members of actinobacteria especially within the plant and soil-inhabiting strains. The notable presence of LAP BGCs in plant-associating actinobacteria was also illustrated. Streptomyces, Amycolatopsis, Kitasatospora and Frankia showed greater potential in RiPP biosynthesis while lanthipeptides and lasso peptides were the most distributed RiPPs. Three cyanobactin BGCs were also detected. Generally evidence of promising ability of actinobacteria to synthesise diverse classes of RiPPs as well as information needed to rationally select appropriate taxa for rational screening of specific RiPPs are presented.