Year: 2026
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide 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 ( Sin IRED) to catalyze the enantioselective reduction of enamides. Through directed evolution, the final optimized Sin IRED-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 by NADPH-mediated hydride transfer process. This work expands the catalytic versatility of IREDs and provides the first known example of IRED-catalyzed reduction of electron-rich enamides.
Source: JACS Au
Authors: Xiao-Qi Liu, Ru Li, Jun-Liang Chen, Ye Li, Long Wei, Hongli Wu, Li Li, Ben-Hong Chen, Ying Wu, Si-Jia Liu, Guang-Xin Lin, Jia-Fang Zhang, Yongxiang Zheng, Chun Zhang, Yun-Fang Yang, Xin Wang, Peng Chen, Zhi-Jun Jia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
OpenAlex ID: W7126024082