Work

Cofactor-independent photo-enzymatic reductions with water mediated by reductive graphene quantum dots

Year: 2025

Type: article

Abstract: Enzymatic reductions catalyzed by reductases, such as aldo/ketoreductases (AKRs), imine reductases, and ene reductases generally depend on the regeneration of nicotinamide cofactors for industrial viability. This usually involves the addition of a cosubstrate and a second enzyme, a dehydrogenase, e.g. glucose / glucose dehydrogenase. For commercial viability it would be more interesting to use water as the sacrificial cosubstrate to supply the necessary hydrogen atoms. This is possible using photocatalytic methods involving precious metal, e.g. Rh and Ru, complexes as electron mediators. A problem associated with photobiocatalysis in general is the weak penetration of ultraviolet or visible light in biological systems. Here we report the unprecedented use of near infrared (NIR) light in combination with a hybrid photoenzyme based on IR responsive reductive graphene quantum dots (rGQDs) that are non-toxic to AKRs. We envisaged that immobilization of the AKR in close proximity to the rGQDs could enable the direct transfer of hydrogen atoms from water to the prochiral ketone substrate without requiring a nicotinamide cofactor. To test this hypothesis, we immobilized rGQDs on the surface of the cross-linked AKR. The resulting rGQD/AKR hybrid photobiocatalyst mediated the synthesis of the pharmaceutical intermediate, (R)-1-[3,5-bis(trifluoromethyl)-phenyl] ethanol ((R)-3,5-BTPE) from the corresponding prochiral ketone, in 82% yield and > 99.99% ee under a 50 mW·cm− 2 IR illumination. This work opens new avenues to create artificial photoenzymes that simplify in vitro biocatalysis and enable the coupling of renewable solar energy and sustainable chemical production. Since infrared light accounts for about half of the energy in the entire solar spectrum its efficient utilization is crucial for sustainable applications of sunlight. We have demonstrated that our hybrid photobiocatalyst can effectively utilize infrared light to catalyze the enzymatic reduction of a prochiral ketone. Since these hybrid photobiocatalysts are insoluble solids they can be readily recovered, recycled and potentially employed in continuous flow operation.

Source: Nature Communications

DOI: 10.1038/s41467-025-61908-6