2024
DOI: 10.1002/bit.28864
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Improving the catalytic performance of carbonyl reductase based on the functional loops engineering

Tao‐Shun Zhou,
Xiang‐Yang Li,
Xiao‐Jian Zhang
et al.

Abstract: Vibegron functions as a potent and selective β3‐adrenergic receptor agonist, with its chiral precursor (2S,3R)‐aminohydroxy ester (1b) being crucial to its synthesis. In this study, loop engineering was applied to the carbonyl reductase (EaSDR6) from Exiguobacterium algae to achieve an asymmetric reduction of the (rac)‐aminoketone ester 1a. The variant M5 (A138L/A190V/S193A/Y201F/N204A) was obtained and demonstrated an 868‐fold increase in catalytic efficiency (kcat/Km = 260.3 s−1 mM−1) and a desirable stereos… Show more

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