De novo design of enantioselective artificial metalloenzyme photocatalysts.

De novo protein design creates artificial metalloenzymes that achieve highly enantioselective photocatalysis with racemic metal complexes.

• Why it matters: Achieving enantioselectivity in photocatalysis within protein scaffolds remains challenging, especially for widely used metal polypyridine catalysts, limiting their application in asymmetric synthesis.
• What they did: The study used generative protein design to create de novo scaffolds that bind photocatalysts, followed by directed evolution to produce efficient, highly enantioselective photocatalysts supporting diverse light-driven reactions.
• The result: The evolved artificial metalloenzymes extend photocatalyst excited-state lifetimes, organize substrates near cofactors, and enable stereocontrol, opening new avenues for non-natural catalytic chemistry.