Electroenzymatic Cascade Enables Amino Acid Synthesis through Simultaneous Nitrite Reduction and NADH Regeneration

Abstract Amino acids are central to life and the chemical industry, yet their sustainable synthesis remains a challenge. An electroenzymatic cascade offers a promising alternative by combining the electron/proton transfer capability of electrocatalysis with the exceptional specificity of biocatalysis. Here we present a conceptually distinct electroenzymatic cascade platform that integrates electrocatalytic nitrogen oxide reduction, NADH regeneration, and enzymatic reductive amination. Using l-glutamate (l-Glu) as a model, we demonstrate that with Cu nanowires as the bifunctional electrocatalyst, the system generates NH4+ and biologically active NADH in situ, driving the production of l-Glu under mild conditions. The coupled cascade not only shifts the reaction equilibrium forward but also provides a favorable orientation and a proton-rich environment for the bioactive cofactor, boosting overall selectivity of bioactive NADH. The modular design allows straightforward adaptation to diverse substrates and electrodes, demonstrating the broad generality of this platform. This work establishes a sustainable and versatile strategy for amino acid synthesis and opens new directions for electroenzymatic production of nitrogen-containing chemicals.