Large-scale insights into the biosynthetic potential of the Bacillus cereus group

Bacterial secondary metabolites (SMs) are a critical source of natural product-derived drugs. However, SM discovery efforts have focused overwhelmingly on Actinomycetes , potentially overlooking other key producers. Here, we explore the biosynthetic potential of the Bacillus cereus group, an underexplored complex of SM producers. Using a combined rule- and machine learning-based approach, we mine an unprecedented number of B. cereus group genomes (n = 9,744) for SM-producing biosynthetic gene clusters (BGCs; n = 200,196). Notably, 158,678 B. cereus group BGCs (78.2%) did not cluster with previously described BGCs, suggesting new chemical scaffolds to be explored. B. pseudomycoides was particularly prolific in terms of its SM production potential (30.8 BGC families/genome, Kruskal-Wallis p < 0.0001), and we identify a previously uncharacterized, B. pseudomycoides -unique peptide. Overall, our study represents the largest survey of B. cereus group biosynthetic potential to date and posits the complex as an under-queried SM resource.