雷斯青霉15α-羟基化左旋乙基甾烯双酮的发酵工艺优化

Optimization of Fermentatioo Process for 15α-Hydroxylation of 18-Methyl-estr-4-ene-3,17-dione by Penicillium Raistrickii

利用雷斯青霉（Penicillium raistrickii）的特异性转化酶对甾体化合物左旋乙基甾烯双酮进行15a-位羟基化，制备了重要的激素药物中间体15a羟基左旋乙基甾烯双酮。以种龄、接种量、投料量、pH值控制、溶氧控制、投料和转化时间等影响因子为对象对其发酵罐二级发酵工艺进行了优化。确定0．2％投料量条件下最优发酵工艺条件为：种龄21h；接种量5％；0～27h，pH值7．5、溶氧40％；27～66h，pH值6．0、溶氧20％；投料时间第30h；转化时间42h。在此条件下，转化率可达65％以上，比优化前提高了11．4％，为药物中间体15a-羟基左旋乙基甾烯双酮的进一步扩大发酵转化以及工业化生产奠定了基础。

An important intermediate of hormone medicines, 15a-hydroxyl-18-methyl-estr-4-ene-3, 17-dione, was obtained by the action of the special enzyme of Penicilliurn raistrickii. The optimization of fermentation conditions, such as seed age, inoculum amount, pH value control,dissolved oxygen control, the feeding point of substrate and transformation time had been investigated. When the inventory rate was 0. 2% ,the optimum fermentation conditions were determined as follows： seed age of 21 h; inoculum amount of 5% ;pH value of 7.5 and dissolved oxygen of 40% during 0-27 h;pH value of 6.0 and dissolved oxygen of 20% during 27% 66 h;the feeding point of substrate at the 30th h, transformation time for 42 h. The conversion rate could be up to 65%, which was increased 11.4% by optimization. It laid a solid foundation for further large scale fermentation and commercial process of 15a-hydroxyl-18-methyl-estr-4-ene-3,17-dione.