NADH-recycling and NADH-free strategies for formate dehydrogenase-driven electrocatalytic CO2 reduction

Abstract

Formate dehydrogenases (FDHs) are highly selective and sustainable biocatalysts for the electrochemical reduction of carbon dioxide (CO₂) to formate, a promising energy carrier and industrial feedstock. However, the requirement for costly NADH, i.e., the reduced form of nicotinamide adenine dinucleotide (NAD⁺), as a cofactor, combined with the relatively sluggish kinetics of NAD-dependent FDHs for CO₂ reduction, remains a significant bottleneck for their large-scale industrial implementation. To address these limitations, this review examines two main strategies. The first focuses on efficient NADH regeneration via photocatalytic, enzymatic, and electrochemical approaches in enzymatic CO₂ reduction systems, thereby reducing overall NADH consumption. The second explores NADH-independent solutions, including the replacement of natural NADH with artificial cofactors, often supported by synergistic strategies such as enzyme immobilization and electron transfer pathway engineering. This approach also involves the development of cofactor-free, direct electron transfer (DET) systems enabled by electrode-enzyme engineering for NAD-independent FDHs. Collectively, these strategies hold promise for overcoming the economic and mechanistic bottlenecks of FDH-based electrocatalytic CO₂ reduction. Insights gained via a more detailed understanding of FDH-catalyzed CO₂ reduction mechanisms are expected to provide valuable guidance for the future design of efficient, scalable, and sustainable CO₂ reduction technologies.