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

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.