Semiartificial Photoelectrochemistry for CO₂-Mediated Enantioselective Organic Synthesis

Photoelectrochemical (PEC) cells are under intensive development for the synthesis of solar fuels, but CO₂ reduction typically only results in simple building blocks such as HCOO^-. Here, we demonstrate that CO₂-converting PEC cells can drive integrated enzymatic domino catalysis to produce chiral organic molecules by using CO₂/HCOO^- as a sustainable redox couple. First, we establish a semiartificial electrode consisting of three enzymes co-immobilized on a high surface area electrode based on carbon felt covered by a mesoporous indium tin oxide (ITO) coating. When applying a mild cathodic potential (-0.25 V vs the reversible hydrogen electrode (RHE)), CO₂ is reduced to HCOO^- using a W-formate dehydrogenase (FDH_NvH) from <i>Nitratidesulfovibrio vulgaris</i> Hildenborough, which then enables the reduction of NAD⁺ to NADH by an NAD⁺-cofactor-dependent formate dehydrogenase from <i>Candida boidinii</i> (FDH_CB). Subsequently, an alcohol dehydrogenase (ADH) uses NADH generated from CO₂/HCOO^- cycling to reduce acetophenone to chiral 1-phenylethanol in good enantiomeric excess (93%) and conversion yields (38%). Depending on the specific ADH (ADH_S or ADH_R), either (<i>S</i>)- or (<i>R</i>)-1-phenylethanol can be synthesized at pH 6 and 20 °C. To illustrate solar energy utilization, we integrate the three nanoconfined enzymes with a PEC platform based on an integrated organic semiconductor photocathode to allow for enantioselective synthesis (at +0.8 V vs RHE) based on a solar fuel device. This proof-of-principle demonstration shows that concepts and devices from artificial photosynthesis can be readily translated to precise and sustainable biocatalysis, including the production of chiral organic molecules using light.