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玫瑰红红链霉菌 TS79 将泼尼松转化为 20β-羟基泼尼松化合物。

Transformation of prednisolone to a 20β-hydroxy prednisolone compound by Streptomyces roseochromogenes TS79.

机构信息

School of Life Sciences, Tsinghua University, Beijing 100084, China.

出版信息

Appl Microbiol Biotechnol. 2011 Nov;92(4):727-35. doi: 10.1007/s00253-011-3382-4. Epub 2011 Jun 14.

Abstract

Prednisolone represents an important compound in pharmaceutical preparations. To obtain more bioactive prednisolone derivatives, the microbial transformation of prednisolone was carried out. The steroid products were assigned by an interpretation of their spectral data using mass spectrometry and proton nuclear magnetic resonance ((1)H NMR) analyses. The product was assigned the chemical structure of 11β, 17α, 20β, 21-tetrahydroxypregna-1,4-diene-3-one (named as 20β-hydroxy prednisolone). The conversion of prednisolone to 20β-hydroxy prednisolone by Streptomyces roseochromogenes TS79 was different from a previous study on the microbial transformation of steroid by this organism, which usually generates a 16α-hydroxy steroid product. The different reaction parameters for maximum conversion of prednisolone were optimized. The analysis revealed that the optimum values of the tested variables were 7.5 mg/ml prednisolone dissolved in DMSO and added to the 24-h pre-culture fermentation culture containing 0.05% MgSO(4) and incubated for 24 h. A conversion of 95.1% of prednisolone was observed, which has the potential to be used in industrial production.

摘要

泼尼松龙是药物制剂中的一种重要化合物。为了获得更具生物活性的泼尼松龙衍生物,对泼尼松龙进行了微生物转化。采用质谱和质子核磁共振波谱(1H NMR)分析对甾体产物进行了谱学数据解析。产物被赋予了 11β,17α,20β,21-四羟基孕甾-1,4-二烯-3-酮(命名为 20β-羟基泼尼松龙)的化学结构。玫瑰孢链霉菌 TS79 将泼尼松龙转化为 20β-羟基泼尼松龙的反应与该菌以往对甾体微生物转化的研究不同,通常会生成 16α-羟基甾体产物。优化了最大转化率下泼尼松龙的不同反应参数。分析表明,测试变量的最佳值为溶解在 DMSO 中的 7.5mg/ml 泼尼松龙,并添加到含有 0.05%MgSO4 的 24 小时预培养发酵培养液中,孵育 24 小时。观察到泼尼松龙的转化率为 95.1%,这具有在工业生产中应用的潜力。

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