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Efficient synthesis of an antiviral drug intermediate using overexpressed short‐chain dehydrogenase and cross‐linked enzyme aggregates stabilization
Journal of Chemical Technology and Biotechnology ( IF 3.4 ) Pub Date : 2020-10-02 , DOI: 10.1002/jctb.6584
Kai Wu 1, 2 , Xiaozhi Hu 3 , Zhijun Yang 1, 2 , Junhai Huang 3 , Xiaojing Wang 2 , Lei Shao 2, 3
Affiliation  

(2R,3S)‐N‐tert‐Butoxycarbonyl‐3‐amino‐1‐chloro‐2‐hydroxy‐4‐phenylbutane (1b) is key for the synthesis of the antiviral drug atazanavir. It can be obtained via the stereoselective bioreduction of (3S)‐3‐(N‐Boc‐amino)‐1‐chloro‐4‐phenyl‐butanone (1a) with short‐chain dehydrogenase/reductase (SDR) (EC 1.1.1.1). To develop a practical and cost‐effective biocatalytic approach with high stability and reusability, an SDR mutant (muSDR) from Novosphingobium aromaticivorans was overexpressed in Escherichia coli cell and immobilized by cross‐linked enzyme aggregates with enhanced stability and high efficiency.

中文翻译:

使用过表达的短链脱氢酶和交联酶聚集体稳定合成抗病毒药物中间体

(2 R,3 S-N-叔-丁氧基羰基-3-氨基-1-氯-2-羟基-4-苯基丁烷(1b)是合成抗病毒药物阿扎那韦的关键。它可以通过(3 S)-3-(N -Boc-氨基)-1-氯-4-苯基丁酮(1a)与短链脱氢酶/还原酶(SDR)的立体选择性生物还原而获得(EC 1.1。 1.1)。为了开发一种具有高稳定性和可重复使用性的实用且具有成本效益的生物催化方法,来自Novosphingobium aromaivorans的SDR突变体(muSDR)在大肠杆菌细胞中过表达,并通过交联的酶聚集体固定化,从而提高了稳定性和效率。
更新日期:2020-10-02
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