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筛选具有11α-羟化酶活性以进行17α-羟基孕酮生物转化的菌株。

Screening for strains with 11α-hydroxylase activity for 17α-hydroxy progesterone biotransformation.

作者信息

Gao Qian, Qiao Yuqian, Shen Yanbing, Wang Min, Wang Xibo, Liu Yang

机构信息

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, People's Republic of China.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, People's Republic of China.

出版信息

Steroids. 2017 Aug;124:67-71. doi: 10.1016/j.steroids.2017.05.009. Epub 2017 May 19.

Abstract

Various corticosteroids are prepared by using 11α,17α-diOH-progesterone (11α,17α-diOH-PROG) as an important intermediate and raw material. Hence, strains that can improve the yields of 11α,17α-diOH-PROG should be screened. Cunninghamella elegans CICC40250 was singled out from five common 11α hydroxylation strains. The reaction parameters of 11α,17α-diOH-PROG production were also investigated. C. elegans CICC40250 could efficiently catalyze the hydroxylation of 17α-hydroxy progesterone (17α-OH-PROG) at C-11α position. This strain could also effectively convert 11α,17α-diOH-PROG at high substrate concentrations (up to 30g/L). After the coenzyme precursor glucose was added, the rate of 11α,17α-diOH-PROG formation reached 84.2%, which was 11.4% higher than that of the control group. Our study established a simple and feasible mechanism to increase 11α,17α-diOH-PROG production levels. This mechanism involves C. elegans CICC40250 that can be efficiently applied to induce the biotransformation of 17α-OH-PROG with a hydroxylation biocatalytic ability.

摘要

多种皮质类固醇是通过使用11α,17α - 二羟基孕酮(11α,17α - diOH - PROG)作为重要中间体和原料制备的。因此,应筛选能够提高11α,17α - diOH - PROG产量的菌株。从五种常见的11α羟基化菌株中挑选出了雅致小克银汉霉CICC40250。还研究了11α,17α - diOH - PROG生产的反应参数。雅致小克银汉霉CICC40250能够有效地催化17α - 羟基孕酮(17α - OH - PROG)在C - 11α位的羟基化反应。该菌株在高底物浓度(高达30g/L)下也能有效地转化11α,17α - diOH - PROG。添加辅酶前体葡萄糖后,11α,17α - diOH - PROG的形成速率达到84.2%,比对照组高11.4%。我们的研究建立了一种简单可行的提高11α,17α - diOH - PROG产量水平的机制。该机制涉及具有羟基化生物催化能力的雅致小克银汉霉CICC40250,可有效地用于诱导17α - OH - PROG的生物转化。

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