Reprogramming Imine Reductases for Enantioselective Reduction of Electron-Rich Enamides.

ABSTRACT: Imine reductases (IREDs) are powerful biocatalysts to afford valuable enantioenriched amines via the stereoselective reduction of imines. While significant progress has been made in expanding their catalytic capabilities, direct reduction of electron-rich alkenes by IREDs remains a formidable challenge and is unprecedented in biology. Here, we report the reprogramming of an IRED from Sinorhizobium (SinIRED) to catalyze the enantioselective reduction of enamides. Through directed evolution, the final optimized SinIRED-V5 variant is able to reduce a variety of enamides and deliver diverse protected chiral amines in up to 97% yield and >99:1 enantiomeric ratio (e.r.). Mechanistic studies suggest a novel synergistic pathway involving enamine-imine tautomerization followed

SUBMITTER: Liu XQ 

PROVIDER: S-EPMC12933363 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature