Cofactor NAD(P)H regeneration inspired by heterogeneous pathways

Biocatalysis can empower chemical, pharmaceutical, and energy industries, where the use of enzymes facilitates low-energy, sustainable methods of producing high-value chemicals and pharmaceuticals that are otherwise impossibly troublesome or costly to obtain. One of the largest classes of enzymes (oxidoreductases, ∼25% of the total) capable of promoting bioreduction reactions is vital for the global pharmaceutical and chemical market because of their intrinsic enantioselectivity and specificity. Enzymatic reduction depends on a coenzyme or cofactor as a hydride source, namely nicotinamide adenine dinucleotide (NADH) or its phosphorylated form (NADPH). Given the high cost, stoichiometric usage, and physical instability of NAD(P)H, a suitable method for NAD(P)H regeneration is essential for practical application. This review summarizes the existing methods for NAD(P)H regeneration, including enzymatic, chemical, homogeneous catalytic, electrochemical, photocatalytic, and heterogeneous catalytic routes. Particular focus is given to recent progress in developing heterogeneous systems with potential significance in terms of process simplicity, cleanliness, and energy and/or cost savings.