Abstract: 

Biocatalysis is an attractive methodology due to its green metrics, combined with its vaunted regio-, chemo-, and stereoselectivity. Amongst biocatalysts, oxidoreductases offer redox transformations to a wide variety of substrates and are thus particularly attractive. Many oxidoreductases depend on a nicotinamide-based cofactors, which introduces high cost and poor atom economy. The native cofactor (i.e., NADH or NADPH), however, can be replaced by nicotinamide cofactor biomimetics (NCBs) to address these issues. Additionally, NCBs can enhance enzyme activity due to their divergent structure. Such capabilities open new possibilities for reactivity and biorthogonality. In addition to replacing NAD(P)H with NCBs, redox cofactors can also be recycled to avoid adding stoichiometric amounts of cofactors. This has been done chemically, enzymatically, and electrochemically. Though useful, each of these methods has disadvantages. This work aims to close these gaps by engineering enhanced NCBs and synthesizing an organic scaffold for the bioelectrocatalytic regeneration of redox cofactors.