Optically active 3-cyclohexene-1-carboxylic acid (CHCA) derivatives are important pharmaceutical intermediates. Due to the special rotatable structure, enantioselective preparation of chiral CHCA is hard to achieve. To identify efficient and enantioselective hydrolases for the biosynthesis of CHCA from methyl 3-cyclohexene-1-carboxylate (CHCM), target-oriented screening from soil samples and gene mining from genome database were explored. All putative hydrolases attempted displayed low enantioselectivity. A hydrolase-producing strain JNU9335 was successfully identified with relatively high enantioselectivity, and was designated as a strain of Acinetobacter sp. according to 16S rDNA sequence and phylogenetic analysis. After optimization, strain JNU9335 could produce 233 U·L‒1 hydrolase with E value of 21. Isooctane/aqueous biphasic system is favorable for the enzymatic resolution of CHCM, the E value of JNU9335 could further be increased to 36. The newly identified JNU9335 could tolerate as high as 1.0 M CHCM, producing (S)-CHCM with ees of 99.6% and isolation yield of 34.7%. This study provides an efficient biocatalyst for the preparation of chiral 3-cyclohexene-1-carboxylic acid derivatives.

译文

:旋光性3-环己烯-1-羧酸(CHCA)衍生物是重要的药物中间体。由于其特殊的可旋转结构,很难实现手性CHCA的对映选择性制备。为了鉴定3-环己烯-1-甲酸甲酯(CHCM)生物合成CHCA的高效和对映选择性水解酶,探索了从土壤样品中进行靶向筛选并从基因组数据库中进行基因挖掘的方法。尝试的所有推定水解酶均显示出低对映选择性。以相对高的对映选择性成功鉴定了产生水解酶的菌株JNU9335,并将其命名为不动杆菌属的菌株。根据16S rDNA序列和系统发育分析。经过优化,菌株JNU9335可以产生233 U·L‒1水解酶,E值为21。能够耐受高达1.0 M CHCM,产生(S)-CHCM的ee为99.6%,分离产率为34.7%。该研究为制备手性3-环己烯-1-羧酸衍生物提供了一种有效的生物催化剂。

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