Bioactive Secondary Metabolites from Bacillus subtilis: A Comprehensive Review.

Bacillus subtilis is widely underappreciated for its inherent biosynthetic potential. This report comprehensively summarizes the known bioactive secondary metabolites from B. subtilis and highlights potential applications as plant pathogen control agents, drugs, and biosurfactants. B. subtilis is well known for the production of cyclic lipopeptides exhibiting strong surfactant and antimicrobial activities, such as surfactins, iturins, and fengycins. Several polyketide-derived macrolides as well as nonribosomal peptides, dihydroisocoumarins, and linear lipopeptides with antimicrobial properties have been reported, demonstrating the biosynthetic arsenal of this bacterium. Promising efforts toward the application of B. subtilis strains and their natural products in areas of agriculture and medicine are underway. However, industrial-scale availability of these compounds is currently limited by low fermentation yields and challenging accessibility via synthesis, necessitating the development of genetically engineered strains and optimized cultivation processes. We hope that this review will attract renewed interest in this often-overlooked bacterium and its impressive biosynthetic skill set.