细胞稀释工艺转化甾体11β-羟基的研究

Study on Steroids 11β-Hydroxylation in Cell-dilution Technology

以相等溶氧速率系数KLa为基础将甾体 11β 羟基细胞稀释转化工艺由 2 5 0ml摇瓶放大到 2L、10L发酵罐。通过对通风量、接种量、种龄等发酵参数的研究 ,确定了细胞稀释转化工艺条件。在 10L发酵罐上 ,转化工艺为二级工艺 ,发酵温度 2 8℃ ,二级种子接种量 15 % ,罐压 0 .0 4～ 0 .0 5MPa ,搅拌转速 180～ 2 0 0r/min ,通风量 7L/min ,稀释比 1∶1,转化周期 2 4h ,氢化可的松转化率 74%～ 77%。测定了转化过程中底物和主产物

On the basis of the equal dissolved oxygen coefficient K L a in the liquid, the cell dilution technology for conversion 11β hydroxylation of steroids was scaled up from 250ml shake flask to 2L and 10L fermentor. The fermentation parameters, such as ventilation volume, seed age, inoculum size were all studied. The two grade fermentation process of cell dilution was established. The process conditions on 10L fermentor are as follow: temperature 28℃,inoculums size 15%,press of fermentor 0.04～0.05MPa,stirring speed 180～200r/min,ventilative volume 7L/min,the ratio of dilution 1∶1,biotransformation periods 24h. The rate of conversion of hydrocortisone was 74%～77%.The percentage change of RSA and hydrocortisone were measured during the course of conversion.