绿僵菌羟基化16α,17α-环氧黄体酮的工艺研究

Study on the Hydroxylation of 16α,17α-epoxyprogesterone by Metarhizium anisopliae

利用绿僵菌在发酵罐中进行16α,17α-环氧黄体酮的11α羟基化存在着菌浓度高、不能实现摇瓶高转化率的问题.从抑制剂、减少营养、稀释菌体等方面对绿僵菌羟基化工艺进行了优化,确定了稀释菌体并补料的新工艺.该工艺比直接投底物工艺的绿僵菌转化率提高了13.51%.

When Metarhizium anisopliae was used to transform 16α,17α-epoxyprogesterone,its mycelium density was too high to repeat the conversion rate in shake-flask.Inhibitor,nutrition reduction and mycelium dilution were studied to decrease mycelium density.The results showed that the optimal process conditions were that after the fermented broth was fermented 48 h,diluting it with same volume aseptic water,then adding 2 %16α,17α-epoxyprogesterone for oxidizing.After oxidizing 8 h and 20 h,feeding 0.5 % glucose separately;after 34 h,feeding 0.5 % glucose and 0.05 % ammonia water.After oxidizing 64 h,the mycelium density maintained at 10～15 g / L,the conversion rate achieved 72.38 %.When using this process in a 100 L stirred-tank bioreactor,the conversion rate was 53.12 % which is 34.11 % higher than that of control,which was 39.61 %.