Bioelectrocatalytic Cofactor Regeneration Coupled to CO₂ Fixation in a Redox-Active Hydrogel for Stereoselective C−C Bond Formation

The sustainable capture and conversion of carbon dioxide (CO₂) is key to achieving a circular carbon economy. Bioelectrocatalysis, which aims at using renewable energies to power the highly specific, direct transformation of CO₂ into value added products, holds promise to achieve this goal. However, the functional integration of CO₂-fixing enzymes onto electrode materials for the electrosynthesis of stereochemically complex molecules remains to be demonstrated. Here, we show the electricity-driven regio- and stereoselective incorporation of CO₂ into crotonyl-CoA by an NADPH-dependent enzymatic reductive carboxylation. Co-immobilization of a ferredoxin NADP⁺ reductase and crotonyl-CoA carboxylase/reductase within a 2,2′-viologen-modified hydrogel enabled iterative NADPH recycling and stereoselective formation of (2S)-ethylmalonyl-CoA, a prospective intermediate towards multi-carbon products from CO₂, with 92±6 % faradaic efficiency and at a rate of 1.6±0.4 μmol cm⁻² h⁻¹. This approach paves the way for realizing even more complex bioelectrocatalyic cascades in the future.