Crystal Structure of EstZF172 Catalyzing Stereoselectively (R)-CNDE in Pregabalin Biosynthesis

文献类型： 外文期刊

第一作者： Liang, Zedong

作者： Liang, Zedong;Sun, Qingyue;Zhang, Xiaojun;Chi, Changbiao;Ma, Xiaojie

作者机构：

期刊名称：ACS OMEGA （ 影响因子：4.3； 五年影响因子：4.4 ）

ISSN： 2470-1343

年卷期： 2025 年 10 卷 21 期

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收录情况： SCI

摘要： Pregabalin has garnered extensive clinical application for the management of neuropathic pain and epilepsy owing to its high efficacy and broad drug concentration range. EstZF172 is a key enzyme in the biosynthesis of pregabalin, capable of stereoselectively catalyzing the production of (R)-CCMA from the key intermediate rac-CNDE. The novel crystal structure of EstZF172 indicates that it contains a highly conserved Ser-Lys-Tyr catalytic triad and belongs to the family VIII2 carboxylesterases. Molecular docking demonstrates that the steric hindrance presented by residues I159 and F239 plays a crucial role in influencing the binding affinity of the chiral substrate (R)-CNDE for the catalytic site. The study provides a structural basis and reference for the stereoselective catalysis of EstZF172 and engineering modification of the key enzyme in the synthesis of pregabalin.

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