摘要
利用赭曲霉(Aspergillus ochraceus)MF010催化甾体化合物17α-羟基黄体酮(1)的11α-羟基化反应,制备11α,17α-二羟基黄体酮(2),优化其生物转化工艺条件。运用Plackett-Burman法筛选影响11α-羟基化反应的因素,结果显示碳氮比和温度的影响显著。通过中心组合实验设计进一步优化这2个因素,得到最佳工艺条件:碳氮比2∶1,温度27.7℃。在此条件下,当1投料量为2%时,其摩尔转化率为86.1%。为提升转化率,向发酵培养基中添加助溶剂,并比较了不同助溶剂对1摩尔转化率的影响。结果表明,在发酵培养基中添加1%二甲基甲酰胺(DMF),1的摩尔转化率可提升至93.3%,较未添加时提高了8.4%。
The bioconversion process for the production of 1 1α,17α-dihydroxyprogesterone from 17α-hydroxyprogesterone using Aspergillus ochraceus were investigated. Plackett-Burman design was applied for the screening of the indexes which had great influences on substrate conversion. As a result, temperature and carbon/nitrogen ratio were selected as the most influential factors. Subsequently, the optimization of these factors was carried out using Box-Behnken design and response surface analysis. The results indicated that the optimal bioconversion conditions which provided the maximum molar conversion efficiency of 17ct-hydroxyprogesterone （86.1%） were as follows： carbon/ nitrogen ratio of 2 ： 1 and temperature of 27.7℃. Different cosolvents were added into the fermentation medium for the further improvement of bioconversion. The results showed that the molar conversion rate of 17α-hydroxyprogesterone would be raised to 93.3% when adding 1% of DMF in the optimal fermentation medium, which was 8.4% higher compared with that without cosolvents.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2017年第8期1125-1130,共6页
Chinese Journal of Pharmaceuticals
