Secondary Metabolite Biosynthesis and Regulatory Role of Sucrose in Bacillus subtilis.

Bacillus subtilis is a powerful microbial platform for producing antimicrobial secondary metabolites, yet carbon metabolism, quorum sensing, stress adaptation, and developmental regulation tightly control their biosynthesis. Carbon sources therefore act not only as nutrients but also as regulatory inputs that determine whether the cell prioritizes biomass formation or secondary metabolism. Excess glucose commonly reinforces carbon catabolite repression and suppresses expensive secondary metabolite synthesis pathways. Sucrose and sucrose-rich substrates such as molasses may provide a more balanced carbon flux that supports growth, precursor supply, and transition-phase metabolite production under specific nutritional and physiological conditions. This review discusses how sucrose metabolized through SacP/SacA dependent pathway, fructose- and glucose-derived central carbon pathways, regulate CcpA-mediated CCR, ComQXPA-ComA quorum sensing, Spo0A-AbrB regulation, stress responses, omics-level reprogramming, and efflux through specialized transporters collectively shape antimicrobial metabolite production in B. subtilis. Special emphasis is given to surfactin, fengycin/plipastatin, bacilysin, and bacillaene production and release, as they are synthesized using NRPS- and PKS systems influenced by carbon-source-dependent regulation. We propose that sucrose acts as a metabolic-regulatory substrate rather than a simple carbon source in regulating secondary metabolite production. This perspective provides a framework for designing molasses-based, low-cost, and scalable fermentation strategies for enhanced antimicrobial production in Bacillus and other microbes.