Angew Chem Int Ed Engl. 2026 Jun 16:e2408585. doi: 10.1002/anie.2408585. Online ahead of print.

ABSTRACT

Microbial artificial photosynthesis offers a promising strategy for light-driven biomanufacturing, yet its efficiency remains limited by the non-selective conversion of photogenerated electrons into metabolically usable reducing power, causing energy dissipation and weak coupling between light capture and metabolic reactions. Here, we report a rational strategy using riboflavin (RF), a membrane-permeable and biocompatible flavin photosensitizer, to selectively channel photonic energy into intracellular NADPH regeneration. Quantum chemical calculations and spectroscopic analyses reveal that light-excited RF exhibits a specific binding affinity and favorable electron transfer trend toward NADP⁺. In vivo, RF activation markedly elevated intracellular NADPH levels and enhanced the synthesis of NADPH-dependent metabolites through NADPH reductase-associated pathways. Transcriptomic and inhibition analyses linked RF-mediated NADPH regeneration to NADP⁺/NADPH redox enzymes rather than glucose-6-phosphate dehydrogenase-mediated flux, while NADH-related redox genes remained largely unaffected, demonstrating the selectivity of this reductive route. Cross-species and multi-product validations consistently reproduced these results, underscoring the generality of this mechanism across distinct NADPH-dependent microbial chassis. This work establishes a mechanistically defined and broadly applicable framework for directing photogenerated electrons into specific cellular reducing equivalents, paving the way for efficient artificial photosynthetic and bioelectrochemical platforms.

PMID:42299068 | DOI:10.1002/anie.2408585