A series of synthetic nicotinamide cofactors were synthesized to replace natural nicotinamide cofactors and promote enoate reductase (ER)-catalyzed reactions without compromising activity or stereoselectivity of the bioreduction process. Conversions and enantioselectivities of up to >99% were obtained for C=C bioreductions and the process was successfully upscaled. Furthermore, high chemoselectivity was observed when employing these nicotinamide cofactor mimics (mNADs) with crude extracts in ER-catalyzed reactions.The asymmetric reduction of conjugated C=C double bonds using enoate reductases (ERs, EC 1.3.1.31) is receiving great interest in preparative organic chemistry.1 § Both authors contributed equally.

To date, water has been poorly studied as the sacrificial electron donor for biocatalytic redox reactions using isolated enzymes. Here we demonstrate that water can also be turned into a sacrificial electron donor to promote biocatalytic redox reactions. The thermodynamic driving force required for water oxidation is obtained from UV and visible light by means of simple titanium dioxide-based photocatalysts. The electrons liberated in this process are delivered to an oxidoreductase by simple flavin redox mediators. Overall, the feasibility of photobiocatalytic, water-driven bioredox reactions is demonstrated.