Novel anti-Prelog stereospecific carbonyl reductases from Candida parapsilosis for asymmetric reduction of prochiral ketones.
Novel anti-Prelog stereospecific carbonyl reductases from Candida parapsilosis for asymmetric reduction of prochiral ketones.
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DOI：
10.1039/c0ob00938e
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发表时间：
2011-06-07
影响因子：
3.2
通讯作者：
Montelione GT
中科院分区：
文献类型：
--
作者：
Nie Y;Xiao R;Xu Y;Montelione GT
生物催化在手性分子合成中的应用，由于其具有环境友好的反应条件和无与伦比的化学选择性、区域选择性和立体选择性，是替代化学途径的最环保的技术之一。我们一直对寻找羰基还原酶和评估它们的底物特异性和立体选择性感兴趣。我们现在报道了在假丝酵母旁裂病中发现的一个基因簇，该基因簇由四个开放阅读框组成，包括三个假定的立体特异性羰基还原酶（scr1、scr2和scr3）和一个醇脱氢酶（cpadh）。新发现的3种立体定向羰基还原酶（SCRs）以NADPH为辅酶，对2-羟基苯乙酮生成(S)-1-苯基-1,2-乙二醇具有较高的催化活性。与CPADH一起，这四种酶都是具有新型抗prelog立体选择性的羰基还原酶。SCR1和SCR3对苯乙酮衍生物和氯取代的2-羟基苯乙酮具有明显的特异性，特别是对具有重要药用潜力的β-酮酯- 4-氯-3-氧丁酸乙酯具有非常高的活性。我们的研究还表明，基因组挖掘是发现新酶的有力工具。
Application of biocatalysis in the synthesis of chiral molecules is one of the greenest technologies for the replacement of chemical routes due to its environmentally benign reaction conditions and unparalleled chemo-, regio-and stereoselectivities. We have been interested in searching for carbonyl reductase enzymes and assessing their substrate specificity and stereoselectivity. We now report a gene cluster identified in Candida parapsilosis that consists of four open reading frames including three putative stereospecific carbonyl reductases (scr1, scr2, and scr3) and an alcohol dehydrogenase (cpadh). These newly identified three stereospecific carbonyl reductases (SCRs) showed high catalytic activities for producing (S)-1-phenyl-1,2-ethanediol from 2-hydroxyacetophenone with NADPH as the coenzyme. Together with CPADH, all four enzymes from this cluster are carbonyl reductases with novel anti-Prelog stereoselectivity. SCR1 and SCR3 exhibited distinct specificities to acetophenone derivatives and chloro-substituted 2-hydroxyacetophenones, and especially very high activities to ethyl 4-chloro-3-oxobutyrate, a β-ketoester with important pharmaceutical potentials. Our study also showed that genomic mining is a powerful tool for the discovery of new enzymes.
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影响因子：
--
作者：
Engelking, H;Pfaller, R;Weuster-Botz, D
通讯作者：
Weuster-Botz, D
影响因子：
2.7
作者：
Nie, Y;Xu, Y;Sun, ZH
通讯作者：
Sun, ZH
DOI：
10.1073/pnas.88.22.10064
发表时间：
1991-11-01
影响因子：
11.1
作者：
GHOSH, D;WEEKS, CM;ORR, JC
通讯作者：
ORR, JC
影响因子：
5.2
作者：
Iwasaki, F;Maki, T;Matsumura, Y
通讯作者：
Matsumura, Y
影响因子：
3.2
作者：
Mueller, Marion;Katzberg, Michael;Hummel, Werner
通讯作者：
Hummel, Werner