Biocatalytic Application of Goodfellowiella coeruleoviolacea Imine Reductase: Enantioselective Synthesis of Cyclic Secondary Amines in Deep Eutectic Solvent‐Based Media
The development of sustainable strategies for accessing optically pure amines is essential for pharmaceutical and fine‐chemical manufacturing. Here, we report the characterization of a newly identified imine reductase from Goodfellowiella coeruleoviolacea (GcIRED) and its application to the asymmetric reduction of cyclic imines in deep eutectic solvent based media. GcIRED displayed excellent catalytic performance in choline chloride/glycerol mixtures, enabling high substrate loadings up to 150 mM while maintaining high conversions and >99% ee toward ( S )‐α‐substituted cyclic secondary amines. Compared to benchmark variants, GcIRED showed superior stability and activity in DES‐containing systems. A fed‐batch strategy further increased productivity, raising the turnover number from 8800 to 41 000 using a single enzyme and cofactor charge. Atomistic computational analyses revealed key NADPH‐anchoring residues and highlighted π−π and T‐shaped interactions between the substrate and the nicotinamide moiety, providing structural insight into productive binding and helping rationalize the catalytic behavior observed experimentally. Overall, this study establishes GcIRED as a robust and versatile biocatalyst for sustainable asymmetric amine synthesis and demonstrates how the integration of DES media can unlock improved performance in biocatalytic processes.