Chembiochem. 2026 May 27;27(10):e70381. doi: 10.1002/cbic.70381.
ABSTRACT
Coenzyme regeneration is essential for oxidoreductase-based biocatalysis, yet integrating enzymatic and photocatalytic systems remains challenging due to ROS-mediated enzyme inactivation. Here, we developed a metabolic-inspired compartmentalization strategy that enables sustainable NAD+/NADH cycling by mimicking the spatial organization of cellular redox metabolism. Glucose dehydrogenase (GDH) was encapsulated within silica nanoparticles, exploiting the intrinsic instability of hydroxyl radicals and their limited diffusion distance to shield the enzyme from TiO2-generated ROS while preserving substrate and cofactor accessibility. The encapsulated GDH maintained catalytic competence and achieved five consecutive coenzyme regeneration cycles, whereas the free enzyme lost activity after a single photocatalytic exposure. Beyond cofactor recycling, NADH generated by this system functioned as an endogenous antioxidant, protecting cells from photocatalytic oxidative stress. This work demonstrates that principles from cellular biochemistry, including compartmentalization and redox homeostasis, can be translated into artificial systems for sustainable biocatalysis and cell protection.
PMID:42178976 | DOI:10.1002/cbic.70381