H2-driven cofactor regeneration with NAD(P) plus -reducing hydrogenases

A large number of industrially relevant enzymes depend upon nicotinamide cofactors, which are too expensive to be added in stoichiometric amounts. Existing NAD(P)H-recycling systems suffer from low activity, or the generation of side products. H2-driven cofactor regeneration has the advantage of 100% atom efficiency and the use of H2 as a cheap reducing agent, in a world where sustainable energy carriers are increasingly attractive. The state of development of H2-driven cofactor-recycling systems and examples of their integration with enzyme reactions are summarized in this article. The O2-tolerant NAD+-reducing hydrogenase from Ralstoniaeutropha is a particularly attractive candidate for this approach, and we therefore discuss its catalytic properties that are relevant for technical applications.