Exploring the potential of Bacillus spp. for secondary metabolite production through genome mining approaches

With the rise of antibiotic resistance along with the increase in the emergence of infectious diseases, the search for new therapeutic agents is of dire need. Bacillus is one of the widely distributed genera of bacteria, which has immense applications in biotechnology, medicine, and environmental protection, and is known to produce a vast range of secondary metabolites (SMs). Using several bioinformatics programming approaches along with phylogenetic and genomic comparisons, biosynthetic gene clusters (BGCs) were characterized from Bacillus reference genome sequences publicly available in databases to obtain new insights into the diversity and distribution of these BGCs in Bacillus for the discovery of unexplored SMs. From this study, average nucleotide identity (ANI) analysis of 87 species shows more than 70% similarities among them, whereas phylogenetic studies show species diversification into 4 clades based on the presence of 1-2 BGC types. High diversity for SMs production was observed in most of the species, where the majority of BGCs types were found to be terpene, nonribosomal peptide synthase (NRPS), polyketide synthase (PKS), hybrid gene clusters, ribosomally synthesized and post translationally modified peptide (RiPP) encoding for different characterized secondary metabolites, along with some unique metabolites characterized based on similarity confidence value. Many uncharacterized BGCs were found distributed within each species, giving new insights into novel compound discovery. These findings will open the door to the identification of species-specific pathways for SM development and contribute to creating new insights into therapeutic systems.