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Efficient biosynthesis of (R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol using a mutant short-chain dehydrogenase from Novosphingobium aromaticivorans
Tetrahedron Letters ( IF 1.5 ) Pub Date : 2020-04-04 , DOI: 10.1016/j.tetlet.2020.151914
Yafeng Zhou , Qiaojun Zhao , Shuyao Zhou , Fandi Que , Guifang Li , Yunping Tang

(R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol ((R)-CPEO) is an important chiral intermediate for antifungal drug synthesis. (R)-CPEO can be produced from 2-chloro-1-(2, 4-dichlorophenyl) ethanone (CPE) via a mutant short-chain dehydrogenase/reductase from Novosphingobium aromaticivorans (NaSDR). The Vmax of a mutant NaSDR-G145A/I199L toward CPE (6.32 U mg−1) was greater than that of wild-type NaSDR (2.58 U mg). The Km of mutant NaSDR-G145A/I199L toward CPE (0.23 mM) was less than that of wild-type NaSDR (0.38 mM), indicating that the substrate affinity of mutant NaSDR-G145A/I199L was the greater of the two. Docking simulations were used to illustrate the mechanisms of the increased enzyme activity of NaSDR-G145A/I199L; these showed that NaSDR-G145A/I199L presented a more effective docking posture than that of the wild-type enzyme. Further, NaSDR-G145A/I199L and glucose dehydrogenase (GDH) were used to transform 120 g/L CPE into (R)-CPEO. After 6 h, the conversion rate and enantiomeric excess values were 99% and 99.95%, respectively. The present study provides a practical method for high substrate loading of (R)-CPEO for industrial-scale applications.



中文翻译:

使用来自新孢子虫芳香族的突变体短链脱氢酶有效地合成(R)-2-氯-1-(2,4-二氯苯基)乙醇

R)-2-氯-1-(2,4-二氯苯基)乙醇((R)-CPEO)是抗真菌药物合成的重要手性中间体。(R)-CPEO可以由2-氯-1-(2,4-二氯苯基)乙酮(CPE)经由芳族新孢子虫Novosphingobium aromaivorans)的突变短链脱氢酶/还原酶(Na SDR)制得。所述的Vmax的突变体的SDR-G145A / I199L朝向CPE(6.32û毫克-1)比野生型更大的Na SDR(2.58û毫克- )。Na SDR-G145A / I199L突变体对CPE的Km(0.23 mM)小于野生型NaSDR(0.38 mM),表明突变型Na SDR-G145A / I199L的底物亲和力是两者中较大的。对接模拟用于说明Na SDR-G145A / I199L酶活性增加的机制。这些表明Na SDR-G145A / I199L呈现出比野生型酶更有效的对接姿势。此外,使用Na SDR-G145A / I199L和葡萄糖脱氢酶(GDH)将120g / L CPE转化为(R)-CPEO。6小时后,转化率和对映体过量值分别为99%和99.95%。本研究为工业规模应用的(R)-CPEO的高底物负载提供了一种实用的方法。

更新日期:2020-04-04
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