免疫抑制剂环孢菌素A高产菌株发酵中试放大研究  

Studies on the Scale-up Fermentation for Immunosuppressant Cyclosporin A of a High-yielding Strain

作　　者：林仙菊 张祝兰[1] 温耀明[1] 严凌斌[1] 邱观荣[1] 黄洪祥[1] 连云阳[1] LIN Xianju;ZHANG Zhulan;WEN Yaoming;YAN Lingbin;QIU Guanrong;HUANG Hongxiang;LIAN Yunyang(Fujian Institute of Microbiology,Fuzhou 350007,China)

机构地区：[1]福建省微生物研究所,福建福州350007

出　　处：《药物生物技术》2025年第1期14-20,共7页Pharmaceutical Biotechnology

基　　金：福建省公益类项目(No.2023R1005002)。

摘　　要：以实验室筛选得到的产环孢菌素A高产菌株雪白白僵菌FIM-1809-7为研究对象,确定其中试发酵放大工艺及生产水平。采用单因素试验研究环孢菌素A最佳发酵工艺条件,并通过中试放大100 L及1吨发酵罐验证其发酵生产水平。结果确定最佳发酵工艺条件:种子菌龄72 h,种子装料系数250 mL每2 L,二级种子接种量0.2%~0.4%,发酵接种量10~15%,发酵pH 5.6,消泡剂泡敌添加量0.05%,发酵周期7 d。并通过5批次中试1吨发酵罐放大生产发酵环孢菌素A,其效价水平略有波动,效价平均值达到11913μg/mL,最高效价值可达到12586μg/mL。通过本试验建立雪白白僵菌FIM-1809-7稳定生产环孢菌素A中试发酵工艺,为环孢菌素A的工业化生产应用奠定了基础。This study aims to determine the pilot-scale fermentation amplification process and production level of Beauveria nivea strain FIM-1809-7 with high yield of Cyclosporin A,that screened in the laboratory.Through the single-factor experiment to study the optimal fermentation process conditions of Cyclosporin A,and its fermentation production level was verified through the pilot-scale amplification in 100 L and 1t fermenters.The results determined the optimal fermentation process conditions as follows:the seed age was 72 hours,the seed loading coefficient was 250 mL/2L,the inoculation amount of the secondary seed was 0.2%~0.4%,the fermentation inoculation amount was 10%~15%,the fermentation pH was 5.6,the addition amount of the antifoaming agent“Paodi”was 0.05%,and the fermentation cycle was 7 days.Moreover,through the amplified production and fermentation of cyclosporin A in 5 batches of 1t fermenters in the pilot scale,the titer level fluctuated slightly,with the average titer reaching 11913μg/mL and the highest titer value reaching 12586μg/mL.Through this experiment,the pilot-scale fermentation process for the stable production of Cyclosporin A by Beauveria nivea FIM-1809-7 was established,laying a foundation for the industrial production and application of Cyclosporin A.

关 键 词：雪白白僵菌 环孢菌素A 免疫抑制剂 发酵 高产 中试放大 

分 类 号：R979.5[医药卫生—药品] Q93[医药卫生—药学]