流加补料技术在林可霉素发酵中的应用  

Application of Flow Feeding Technology to Lincomycin Fermentation

作　　者：李继安[1] 林惠敏[1] 牛金刚[2] 张宏周[2] 陈代杰 

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 [2]河南天方药业股份有限公司,河南驻马店463003 [3]中国医药工业研究总院,上海200040

出　　处：《中国医药工业杂志》2012年第9期739-742,共4页Chinese Journal of Pharmaceuticals

基　　金：国家"重大新药创制"科技重大专项(2010ZX09401-403);国家自然科学基金(81072557;91172962);上海市自然科学基金(09ZR1430800);上海市青年科技启明星计划(B类)(11QB1406300)

摘　　要：前期摇瓶预试验表明林可霉素(1)发酵过程中存在葡萄糖效应,整个发酵代谢过程特别是发酵前期耗氧量较高,于是在200 L发酵罐中针对上述两点进行了工艺优化。发酵中后期通过流加葡萄糖和硫酸铵解除葡萄糖效应,同时稳定1产生菌的发酵代谢环境,使整个发酵过程的菌丝形态呈现良好的新老接替,解决了1产生菌产抗后劲不足的问题。同时在流加补料工艺中延长了发酵周期,使1发酵放罐效价较分批补料工艺提高了50.3%,比目前国内1放罐的平均效价(7 500 g/ml)提高了91.1%。According to the preliminary pre-test in shake flasks, it could be concluded that there was a glucose effect in the fermentation of lincomycin （1）. Furthermore, the high oxygen consumption was found in the whole fermentation process. This event was specially strong in the prophase of the fermentation. Based on above facts, the fermentation process was optimized in a 200 L fermentor. As a result, the glucose and ammonium sulfate were fed with continuous flow to remove the glucose effect and keep a stable fermentation process in the middle and late phase of the fermentation. The process of mycelium regeneration became better in whole fermentation. This study prolonged fermentation period and increased the production of 1 in the fermentation anaphase. With the continuous flow feeding technology, the production of 1 increased by 50.3 % compared with the repeated-batch feeding. The final fermentation units of 1 was 91.1% higher than the present average titer （7 500 μg/ml） of the other Chinese manufacturer.

关 键 词：林可霉素 流加补料 分批补料 发酵 

分 类 号：TQ465[化学工程—制药化工]