游动放线菌产雷帕霉素的发酵工艺改进  

Improvement of Fermentation Technology of Rapamycin by Actinoplanes sp.

作　　者：陈昌发[1] 黄鹤[1] 张长清[1] 胡海峰[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院,创新药物与制药工艺国家重点实验室,上海200040

出　　处：《中国医药工业杂志》2014年第10期925-928,共4页Chinese Journal of Pharmaceuticals

基　　金：国家"重大新药创制"科技重大专项(2014ZX09201001-012);上海市科技支撑项目(12431901102)

摘　　要：以游动放线菌Actinoplanes sp.SIPI-8011为出发菌株,通过优化其发酵培养基组分及含量,促进雷帕霉素的合成。结果显示,培养基中添加甘油作为碳源,并分阶段控制pH值,能够提高雷帕霉素产量,而添加甜菜碱能够减少副产物27-O-去甲基雷帕霉素的生成。于50 L发酵罐上进行放大培养,结果显示,在优化工艺下,50 L发酵罐中雷帕霉素的产量为920ug/ml,比原工艺提高了38.8%,27-O-去甲基雷帕霉素含量较优化前减少了83.5%。The fermentation medium composition was optimized in flasks to improve the production of rapamycin by Actinoplanes sp. SIPI-8011. The results showed that it could increase the productivity of rapamycin by adding glycerol as the carbon resource, as well as controlling pH value during the period. Meanwhile, it could reduce the formation of the byproduct 27-O-demethylrapamycin by adding betaine. The improved medium was investigated in a 50 L jar-fermentor, and the titre of rapamycin reached 920 μg/ml, which was a 38.8 % increase compared to the original conditions. The amount of 27-O-demethylrapamycin was reduced by 83.5 % at the same time.

关 键 词：免疫抑制剂 雷帕霉素 27-O-去甲基雷帕霉素 发酵 

分 类 号：TQ465[化学工程—制药化工]