Biocatalytic cofactor regeneration for CO2 reduction: Integration of a hydrogenase and a formate dehydrogenase in H2-driven systems

Formate dehydrogenases catalyze the reversible oxidation of formate to carbon dioxide. These enzymes play an important role in CO₂ reduction and serve as nicotinamide cofactor recycling enzymes. More recently, the CO₂-reducing activity of formate dehydrogenases, especially metal-containing formate dehydrogenases, has been further explored for efficient atmospheric CO₂ capture. In this sense, molecular hydrogen (H₂) as the fuel of the future represents an efficient, cheap and environmentally friendly reducing agent when produced from renewable sources. Hydrogenases are enzymes that catalyze the reversible oxidation of H₂. Herein, the functional interplay between the soluble [NiFe] hydrogenase from Cupriavidus necator and the molybdenum-dependent formate dehydrogenase from Rhodobacter capsulatus was investigated in a coupled biocatalytic system. H₂-driven CO₂ reduction (H₂CO₂R) using methyl viologen as an artificial electron mediator gave a higher product yield of formate than using NAD⁺ as the physiological electron mediator. The enzymes were stable under anaerobic conditions for 18 h, making the coupled reaction suitable for biotechnological purposes.