Evaluation of lipases for chemo-enzymatic synthesis of molnupiravir

Biocatalysis has emerged as a sustainable and highly selective method for synthesizing active pharmaceutical ingredients (APIs). This study investigated the potential of various lipases as biocatalysts in a novel two-step mediated process to optimize the production of the antiviral drug molnupiravir. 21 commercial lipases from 13 different organisms were evaluated. While lipases from Candida antarctica (CALB), Rhizopus oryzae, and Thermomyces lanuginosus successfully synthesized molnupiravir, only CALB achieved acceptable yields. Notably, immobilized CALB demonstrated significant activity, whereas its free form resulted in substantially lower yields. These findings underscore the critical impact of enzyme preparation on biocatalytic efficiency. The results suggest that biocatalyst screening protocols must consider both free and immobilized forms as primary variables to ensure that viable enzymes are not prematurely overlooked due to their preparation state.