Facile Asymmetric Syntheses of Non-Natural Amino Acid (<i>S</i>)-Cyclopropylglycine by the Developed NADH-Driven Biocatalytic System

作者全名：Tang, Qian; Li, Shanshan; Zhou, Liping; Sun, Lili; Xin, Juan; Li, Wei

作者地址：[Tang, Qian] Chongqing Med & Pharmaceut Coll, Sch Pharm, 82 Middle Coll City Rd, Chongqing 401331, Peoples R China; [Li, Shanshan; Zhou, Liping; Sun, Lili; Xin, Juan; Li, Wei] Chongqing Med Univ, Sch Pharm, Dept Med Chem, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China

通信作者：Li, W (通讯作者)，Chongqing Med Univ, Sch Pharm, Dept Med Chem, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.

来源：CATALYSTS

ESI学科分类：CHEMISTRY

WOS号：WOS:001233306800001

JCR分区：Q2

影响因子：3.8

年份：2024

卷号：14

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：(S)-cyclopropylglycine; bifunctional enzyme; coenzyme regeneration; reductive amination; asymmetric synthesis

摘要：A self-sufficient bifunctional enzyme integrating reductive amination and coenzyme regeneration activities was developed and successfully employed to synthesize (S)-cyclopropylglycine with an improved reaction rate 2.1-fold over the native enzymes and a short bioconversion period of 6 h at a high substrate concentration of 120 g<middle dot>L-1 and space-time yield of (S)-cyclopropylglycine up to 377.3 g<middle dot>L-1<middle dot>d(-1), higher than that of any previously reported data. Additionally, (S)-cyclopropylglycine could be continuously synthesized for 90 h with the enzymes packed in a dialysis tube, providing 634.6 g of (S)-cyclopropylglycine with >99.5% ee and over 95% conversion yield up to 12 changes. These results confirmed that the newly developed NADH-driven biocatalytic system could be utilized as a self-sufficient biocatalyst for industrial application in the synthesis of (S)-cyclopropylglycine, which provides a chiral center and cyclopropyl fragment for the frequent synthesis of preclinical/clinical drug molecules.

基金机构：Municipal Science and Technology Committee of Chongqing [cstc2021jcyj-msxmX0212]

基金资助正文：This research was funded by Municipal Science and Technology Committee of Chongqing: cstc2021jcyj-msxmX0212.