ABSTRACT The C‐20 hydroxyl substituent is a crucial moiety in various steroid drugs, yet its chemical synthesis has long been hampered by challenges such as poor atom economy and stereoselectivity. To address these issues, we herein identified a carbonyl reductase ( Lf CR) from Limosilactobacillus fermentum that catalyzes the stereo‐ and regioselective reduction of C‐20 ketones for R ‐type sterol synthesis. Integrated with a two‐phase system and cofactor regeneration system, this method enables the regio‐ and stereoselective reduction of C‐20 ketone group in commercial steroid ketones and is directly scalable to gram‐scale production, achieving up to 91% isolated yield. Furthermore, this method can achieve a substrate loading capacity of 50 g L −1 20β‐hydroxyprogesterone (20β‐DHP), and yield product concentration of 36 g L −1 and turnover frequency of 282 h −1 . This study establishes an efficient and scalable biocatalytic route for the highly selective and cost‐effective synthesis of sterols.
WANG et al. (Mon,) studied this question.