Systematic Categorization and Functional Diversity of Secondary Metabolites from Bacillus spp.: A Review.

Microbial secondary metabolites shape interactions across agricultural, food, and clinical settings, and many have seeded modern antimicrobial discovery. Bacillus species are particularly prolific producers, encoding biosynthetic systems that generate chemically diverse metabolite families, ranging from lipopeptides and peptides to macrolactones, organic acids, polyketides, and squalenes with activities that extend beyond growth inhibition to antibiofilm effects, signaling, and host-relevant phenotypes. Here we systematically categorize Bacillus-derived secondary metabolites based on biosynthetic logic and chemical scaffolds, synthesize current understanding of their modes of action, and highlight representative structure-function relationships that explain potency, spectrum, and context dependence. We further discuss practical considerations that constrain translation, including metabolite heterogeneity in complex mixtures, yield and manufacturability, cytotoxicity and stability, and challenges in assigning causality to specific compounds in vivo. Finally, we outline emerging opportunities leveraging genome mining, metabolomics-enabled dereplication, and synthetic biology. These approaches allow for the prioritization of promising metabolites and the tailoring of their deployment across agriculture, food systems, and medicine. By linking chemical architecture to biological function, this review provides a framework for rational selection and application of Bacillus metabolites in diverse applied contexts.