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Fine tuning the enantioselectivity and substrate specificity of alcohol dehydrogenase from Kluyveromyces polysporus by single residue at 237
Catalysis Communications ( IF 3.4 ) Pub Date : 2018-01-13 , DOI: 10.1016/j.catcom.2018.01.012
Yue Wang , Wei Dai , Yongmei Liu , Zhongwei Zhang , Jieyu Zhou , Guochao Xu , Ye Ni

Here, S237 was identified to be important in fine tuning the substrate specificity and enantioselectivity of alcohol dehydrogenase from Kluyveromyces polysporus (KpADH). In the reduction of a diaryl ketone, (4-chlorophenyl)-(pyridin-2-yl)-methanone (1a), the highest and lowest enantioselectivity of 96.1% and 27.0% e.e. (R) were obtained with S237A and S237C. Kinetic parameters analysis revealed that S237G, S237A, S237H and S237D displayed improved kcat/Km toward 1a. Various prochiral ketones, including acetophenone, 4-chloroacetophenone and ethyl 2-oxo-4-phenylbutyrate could be asymmetrically reduced by S237C, S237G and S237E with > 99% e.e. This study provides guidance for the application of KpADH in the preparation of chiral secondary alcohols.



中文翻译:

通过237个单一残基精细调节多孢酵母醇脱氢酶的对映选择性和底物特异性。

在这里,S237被认为对微调多孢克鲁维酵母Kp ADH)的醇脱氢酶的底物特异性和对映选择性很重要。在二芳基酮(4-氯苯基)-(吡啶-2-基)-甲酮(1a)的还原中,用S237A和S237C获得最高和最低对映选择性,分别为96.1%和27.0%eeR)。动力学参数分析表明,S237G,S237A,S237H和S237D的k cat / K m值1a方向提高。ee > 99%ee的S237C,S237G和S237E可以不对称还原包括乙酰苯,4-氯苯乙酮和2-氧代-4-苯基丁酸乙酯在内的各种手性酮。该研究为Kp ADH在手性仲代制备中的应用提供了指导酒精。

更新日期:2018-01-13
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