Semi‐Artificial Photosynthesis Enables Light‐Driven Biomanufacturing in Non‐Photosynthetic Bacteria

ABSTRACT Semiconductor biohybrid systems integrate microbial biosynthesis with semiconductor light harvesting to sustainably power energy‐intensive chemical production. Although such systems have been widely explored in photosynthetic bacteria, extending them to non‐photosynthetic biomanufacturing chassis such as Bacillus subtilis ( B. subtilis ) remains substantially more challenging, owing to peptidoglycan‐induced nanoparticle aggregation and mass‐transfer limitations, cytotoxicity, and inefficient interfacial electron transfer from loose adsorption between inorganic semiconductors and cells. Here, we propose a non‐invasive enhancement strategy that leverages the endogenous hydrogen sulfide (H 2 S) pathway of the B. subtilis host and couples it with semiconductor materials to construct a semi‐artificial photosynthetic biohybrid system. This system harnesses light energy to enhance endogenous nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) regeneration, thereby augmenting microbial production without genetic modification of the target biosynthetic pathways. Applied to engineered B. subtilis for 2’‐fucosyl lactose (2’‐FL) and surfactin production, the biohybrid system increases product titres by two‐ to three‐ fold. This strategy, integrated with metabolic engineering, is effective for rapid and enhanced chemical synthesis in B. subtilis , with potential applicability to other non‐photosynthetic bacteria harboring endogenous H 2 S pathways.