| Summary: | Chiral tertiary alcohols are important organic compounds in science as well as in industry. However, their preparation in enantiomerically pure form is still a challenge due to their complex structure and steric hindrances compared with primary and secondary alcohols, so kinetic resolution could be an attractive approach. Lipase A from Candida antarctica (CAL‐A) has been shown to catalyze the enantioselective esterification of various tertiary alcohols with excellent enantioselectivity but low activity. Here we report a mutagenesis study by rational design to improve CAL‐A activity against tertiary alcohols. Single mutants of CAL‐A were selected, expressed, immobilized and screened for esterification of the tertiary alcohol 1,2,3,4‐tetrahydronaphthalene‐1‐ol. A double mutant V278S+S429G showed a 1.5‐fold higher reaction rate than that of the wild type CAL‐A, while maintaining excellent enantioselectivity.
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