Revisiting Horseradish Peroxidase-Catalyzed Aerobic Oxidation of NAD(P)H in the Presence of Mn(II) and Mediators: Application in Catalytic Oxidation

Aerobically oxidative regeneration of NAD(P)+ is attractive to drive dehydrogenase (DH)-catalyzed oxidation. In this work, horseradish peroxidase (HRP)-catalyzed aerobic oxidative recycling of NAD(P)+ was revisited in the presence of Mn2+ and mediators. The chemobiocatalytic cofactor regeneration system was not only efficient but also exhibited a broad substrate scope. Besides HRP, other hemoproteins including myoglobin and hemoglobin enabled NADH to be oxidized by O2 in the presence of Mn2+ and mediators, despite much lower efficiencies. A putative mechanism was proposed. More importantly, the practicability of the cofactor recycling system was demonstrated in the synthesis of carboxylic acids from aldehydes by integrating it with an aldehyde DH (ALDH), with yields of up to 99%. The preparative-scale production of important biobased furancarboxylic acids was performed, with isolated yields of >93% and total turnover numbers for HRP of up to 210,000. Besides, it may be applicable in (chemo)biocatalytic cascade oxidation processes involving multiple nicotinamide cofactors. However, it was found that this protocol suffered from the gradual losses of enzymatically active NAD(H) during oxidative regeneration.