Iridium Artificial Metalloenzymes Enabled Photo‐Enzymatic Radical Indolone Synthesis

Biotin–streptavidin artificial metalloenzymes (ArMs) provide a platform to integrate transition‐metal catalysis within a protein‐defined microenvironment. Traditional indolone syntheses often rely on transition metal catalysts, high temperatures, and strong oxidants, limiting functional‐group tolerance, and sustainability. In this study, we report a visible‐light‐driven radical cyclization of acrylamides and diazo‐esters to indolones mediated by a biotinylated iridium‐photocatalyst. Incorporation into engineered streptavidin generates highly active photo‐ArMs, enabling reactions under mild aqueous conditions at 0.01 mol% Ir loading, broad substrate scope, and TONs up to 6300. Confinement of the iridium center within the protein binding pocket enhances turnover efficiency, establishing indolone formation as a new transformation accessible via biotin–streptavidin ArMs and highlighting their potential as sustainable platforms for bioactive motif synthesis.