Bioelectrocatalysis with a palladium membrane reactor

Enzyme catalysis is used to generate approximately 50,000 tons of value-added chemical products per year. Nearly a quarter of this production requires a stoichiometric cofactor such as NAD⁺/NADH. Given that NADH is expensive, it would be beneficial to regenerate it in a way that does not interfere with the enzymatic reaction. Water electrolysis could provide the proton and electron equivalent necessary to electrocatalytically convert NAD⁺ to NADH. However, this form of electrocatalytic NADH regeneration is challenged by the formation of inactive NAD₂ dimers, the use of high overpotentials or mediators, and the long-term electrochemical instability of the enzyme during electrolysis. Here, we show a means of overcoming these challenges by using a bioelectrocatalytic palladium membrane reactor for electrochemical NADH regeneration from NAD⁺. This achievement is possible because the membrane reactor regenerates NADH through reaction of hydride with NAD⁺ in a compartment separated from the electrolysis compartment by a hydrogen-permselective Pd membrane. This separation of the enzymatic and electrolytic processes bypasses radical-induced NAD⁺ degradation and enables the operator to optimize conditions for the enzymatic reaction independent of the water electrolysis. This architecture, which mechanistic studies reveal utilizes hydride sourced from water, provides an opportunity for enzyme catalysis to be driven by clean electricity where the major waste product is oxygen gas.