A Trifunctional Imine Reductase Enables a Three‐Step Biocatalytic Cascade
Abstract
Traditional biocatalytic cascades typically require discrete enzymes for each synthetic step. Here, we report unprecedented trifunctional imine reductases (IRED) that conduct three sequential transformations-alkene reduction, intramolecular reductive amination, and imine reduction-all within a single catalytic cycle. This elegant single-enzyme catalytic system directly transforms linear substrates into enantiomerically pure 2-aryl pyrrolidines via a concerted cascade without intermediate isolation. Combining density functional theory (DFT) calculations and mechanistic studies, we elucidate how the IRED achieves step-selective catalysis. Our findings establish a proof-of-concept for simplifying complex biocatalytic cascades using multifunctional enzymes, offering a powerful strategy to streamline synthetic pathways.
Fields of Study & Subjects
Enzyme Catalysis and Immobilization
Cyclopropane Reaction Mechanisms
Asymmetric Hydrogenation and Catalysis
Publication details
- Journal / source
- ChemBioChem
- Publisher
- Wiley
- Volume
- 27
- Issue
- 2
- Pages
- e202500838–e202500838
- Publication date
- 1 January 2026
- Language
- EN