产诺加霉素链霉菌摇瓶发酵条件的研究  

The Studies of the Flask Fermentation Condition of Streptomyces Nogalater Producing Nogalamycin

作　　者：刘伟[1] 石煊雯[1,2] 李梦茜[1,2] 李继安[1] 陈代杰[1] 邵雷[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 [2]上海师范大学生物工程学院,上海200234

出　　处：《药物生物技术》2013年第1期39-43,共5页Pharmaceutical Biotechnology

基　　金：国家自然科学基金(No.81172962);上海市青年科技启明星计划(No.11QB1406300);国家"重大新药创制"科技重大专项(No.2009ZX09301-007)

摘　　要：诺加霉素是由黑胡桃链霉菌Streptomyces nogalater产生的结构复杂的蒽环类抗生素,具有较强的抗肿瘤活性。该文对实验室保藏的Streptomyces nogalater ATCC 27451进行菌种选育,得到了一株发酵效价高,遗传稳定的高产菌株。通过摇瓶培养,从发酵培养基和培养条件两方面进行发酵工艺的优化。培养基方面,从单一碳源,单一氮源的最佳种类和组合的筛选,到前体氨基酸以及油的添加进行尝试;培养条件方面,考察了温度,pH,装量,放瓶时间等因素,最终获得的最佳培养基和培养条件,与出发初始菌株和初始培养条件相比,从最初的发酵产量0.048 g/L提高到了0.312 g/L,最终发酵单位提高了6.5倍。这些工作为我们以后大规模的发酵诺加霉素奠定了基础。Nogalamycin, a potential antitumor anthracycline drug, produced by Streptomyces nogalater, has the complicated structureand the high antitumor activity. In the structure, there is a unique glycosylation and a C-C ring. Through natural separation of Streptomyces nogalater ATCC 27451, the high-yield strain,which is genetically stabled was obtained. Furthermore, the fermentation medium such as the carbon sources, the nitrogen sources and precursor amino acid, oil were optimized. Then were optimized culture conditions like fermentation temperature, fermentation pH value, et al. Compared with the initial strains and culture conditions, the final fermentation units were increased by 6. 5 times from 0. 048 g/L to 0. 312 g/L.

关 键 词：蒽环类抗生素 抗肿瘤抗生素 诺加霉素 菌种选育 培养基优化 摇瓶发酵 

分 类 号：TQ465[化学工程—制药化工] Q815[生物学—生物工程]