AUTHOR=Yin Qun-Jian , Ying Ti-Ti , Zhou Zhen-Yi , Hu Gang-Ao , Yang Cai-Ling , Hua Yi , Wang Hong , Wei Bin 

TITLE=Species-specificity of the secondary biosynthetic potential in Bacillus

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1271418

DOI=10.3389/fmicb.2023.1271418

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>Although <italic>Bacillus</italic> species have produced a wide variety of structurally diverse and biologically active natural products, the secondary biosynthetic potential of <italic>Bacillus</italic> species is widely underestimated due to the limited number of biosynthetic gene clusters (BGCs) in this genus. The significant variation in the diversity and novelty of BGCs across different species within the <italic>Bacillus</italic> genus presents a major obstacle to the efficient discovery of novel natural products from <italic>Bacillus</italic>.</p></sec><sec><title>Methods</title><p>In this study, the number of each class of BGCs in all 6,378 high-quality <italic>Bacillus</italic> genomes was predicted using antiSMASH, the species-specificity of BGC distribution in <italic>Bacillus</italic> was investigated by Principal component analysis. Then the structural diversity and novelty of the predicted secondary metabolites in <italic>Bacillus</italic> species with specific BGC distributions were analyzed using molecular networking.</p></sec><sec><title>Results</title><p>Our results revealed a certain degree of species-specificity in the distribution of BGCs in <italic>Bacillus</italic>, which was mainly contributed by siderophore, type III polyketide synthase (T3PKS), and transAT-PKS BGCs. <italic>B. wiedmannii</italic>, <italic>B. thuringiensis</italic>, and <italic>B. cereus</italic> are rich in RiPP-like and siderophore BGCs, but lack T3PKS BGCs, while <italic>B. amyloliquefaciens</italic> and <italic>B. velezensis</italic> are abundant in transAT-PKS BGCs. These <italic>Bacillus</italic> species collectively encode 77,541 BGCs, with NRPS and RiPPs being the two most dominant types, which are further categorized into 4,291 GCFs. Remarkably, approximately 54.5% of GCFs and 93.8% of the predicted metabolite scaffolds are found exclusively in a single <italic>Bacillus</italic> species. Notably, <italic>B. cereus</italic>, <italic>B. thuringiensis</italic>, and <italic>B. velezensis</italic> exhibit the highest potential for producing species-specific NRPS and PKS bioinformatic natural products. Taking two species-specific NRPS gene clusters as examples, the potential of <italic>Bacillus</italic> to synthesize novel species-specific natural products is illustrated.</p></sec><sec><title>Conclusion</title><p>This study highlights the species-specificity of the secondary biosynthetic potential in <italic>Bacillus</italic> and provides valuable insights for the targeted discovery of novel natural products from this genus.</p></sec>