Synergistic integration of photoelectron utilization and by-product pathway suppression for microbial production of bacitracin

Bacitracin is renowned for its broad-spectrum antimicrobial activity and low propensity to induce resistance. However, how to achieve efficient bacitracin production remains a significant challenge. In this study, we developed a Bacillus licheniformis -CdSe biohybrid system that operates under sunlight, employing dual regulatory strategies of "increasing incomes" and "cutting expenses" to achieve efficient bacitracin production. For the increasing incomes strategy: CdSe converted solar energy into photoelectrons, providing B. licheniformis with additional energy and accelerating intracellular energy metabolism; For the cutting expenses strategy: Light exposure induced a metabolic pathway rearrangement in B. licheniformis , suppressing the pathway of pulcherrimin synthesis, thereby conserving energy and redirecting resources toward bacitracin synthesis. By integrating these two regulatory strategies, the bacitracin yield exhibited a remarkable increase, achieving a cumulative concentration of 390.9 mg·L −1 within 24 h. Comprehensive analyses, including biochemistry, electrochemistry, proteomics, and transcriptomics, demonstrated that light optimizes energy allocation by suppressing metabolic byproducts in B. licheniformis , thereby enhancing selectivity for the target product. CdSe efficiently harvested solar energy, accelerating intracellular regeneration of ATP and NAD( P )H, and promoting the production of precursor amino acids, ultimately boosting bacitracin synthesis. This study provides insight into how to design microbe-semiconductor biohybrid systems for the sustainable synthesis of high-value chemicals.