Highly selective anti-Prelog synthesis of optically active aryl alcohols by recombinant Escherichia coli expressing stereospecific alcohol dehydrogenase
Highly selective anti-Prelog synthesis of optically active aryl alcohols by recombinant Escherichia coli expressing stereospecific alcohol dehydrogenase
复制标题
表达立体特异性醇脱氢酶的重组大肠杆菌高选择性抗 Prelog 合成光学活性芳醇
DOI：
10.1080/10826068.2015.1045611
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发表时间：
2016
影响因子：
2.9
通讯作者：
Xu Yan
中科院分区：
文献类型：
--
作者：
Li Ming;Nie Yao;Mu Xiao Qing;Zhang Rongzhen;Xu Yan
摘要生物催化不对称合成作为重要的药物活性中间体和前体，已被广泛应用于光学活性手性醇的合成。然而，涉及抗Prelog特异性醇脱氢酶的可用全细胞系统仍然有限。建立了一个表达近平滑假丝酵母（Candida parapsilosis）抗Prelog立体专一性醇脱氢酶的重组大肠杆菌（Escherichia coli）全细胞系统，用于催化芳基酮不对称还原为抗Prelog构型醇。以2-羟基苯乙酮为底物，pH值、细胞状态和底物浓度等因素对全细胞生物催化的效果有明显影响，木糖是细胞内辅因子再生的有效辅助底物，利用木糖再生（S）-1-苯基-1，2-乙烷酮，光学纯度达到97%e.e.在底物浓度为5g/L时，产率为89%。此外，还考察了重组细胞对不同芳基酮的反应可行性，得到了光学纯度大于95%e. e.的手性醇产物.因此，重组立体专一性醇脱氢酶的全细胞体系可作为一种高效的生物催化剂用于光学活性芳香醇的高对映选择性反Prelog合成，在医药工业中具有广阔的应用前景。
ABSTRACT Biocatalytic asymmetric synthesis has been widely used for preparation of optically active chiral alcohols as the important intermediates and precursors of active pharmaceutical ingredients. However, the available whole-cell system involving anti-Prelog specific alcohol dehydrogenase is yet limited. A recombinant Escherichia coli system expressing anti-Prelog stereospecific alcohol dehydrogenase from Candida parapsilosis was established as a whole-cell system for catalyzing asymmetric reduction of aryl ketones to anti-Prelog configured alcohols. Using 2-hydroxyacetophenone as the substrate, reaction factors including pH, cell status, and substrate concentration had obvious impacts on the outcome of whole-cell biocatalysis, and xylose was found to be an available auxiliary substrate for intracellular cofactor regeneration, by which (S)-1-phenyl-1,2-ethanediol was achieved with an optical purity of 97%e.e. and yield of 89% under the substrate concentration of 5 g/L. Additionally, the feasibility of the recombinant cells toward different aryl ketones was investigated, and most of the corresponding chiral alcohol products were obtained with an optical purity over 95%e.e. Therefore, the whole-cell system involving recombinant stereospecific alcohol dehydrogenase was constructed as an efficient biocatalyst for highly enantioselective anti-Prelog synthesis of optically active aryl alcohols and would be promising in the pharmaceutical industry.