微生物转化法生产度洛西汀中间体手性醇菌株的鉴定

Identification of the fungus capable of biotransforming N, N-dimethyl-3-keto-3-(2-thienyl)-1-prapanamine

摘要:

【目的】获得以DKTP为底物合成度洛西汀关键中间体手性醇(S)-DHTP的菌株。【方法】采用常规及改进的微生物转化法从土壤中进行筛选。【结果】筛选获得一株菌株, 能够将底物DKTP对映选择性地还原为(S)-DHTP, 且具有较高的转化率(>90%)和几乎绝对的对映体过量值(e.e.>99%), 改进的筛选方法更为简便高效。形态学特征和26S rDNA序列分析综合判断, 该菌株属于红酵母属, 命名为红酵母Rhodotorula sp. 507。【结论】供试菌株能够高效地、不对称地生物还原DKTP成度洛西汀前体物(S)-DHTP, 使大量获得度洛西汀前体原料变得经济可行。

Abstract:

[Objective] To obtain a fungus capable of reducing N, N-dimethyl-3-keto-3- (2-thienyl)-1-propanamine (DKTP) to (S)-DHTP, a key precursor to synthesize Duloxetine. [Methods] Routine and an improved biotransformation method were used to screen fungus from soil, and the type of the fungus was identified by analysis of morphological characters and DNA sequence of 26S rDNA. [Results] A fungus was obtained which was capable of asymmetrically reduce DKTP to (S)-DHTP with high yield (more than 90%) and high enanti-ometric excess (more than 99%), and the improved method was more convenient and efficient. The identification showed that the fungus belong to the Genus of Rhodotorula Harrison, and was named as Rhodotorula sp. 507. [Conclusion] The screened fungus could efficiently and asymmetrically reduce DKTP to (S)-DHTP, which makes it possible to get enough precursor for the synthesis of Duloxetine easily and economically.