四羟基环孢菌素衍生物转化菌株发酵条件优化  

Optimization of fermentation conditions for the conversion of [γ-HyMeLeu^4]CyA

作　　者：章丽[1] 戴梦[1] 郑桂珍[1] 赵颖[1] 刘静[1] 张佳[1] 王富强[1] 

机构地区：[1]华北制药集团新药研究开发有限责任公司,河北省工业微生物代谢工程技术研究中心,石家庄050015

出　　处：《中国抗生素杂志》2014年第4期249-252,共4页Chinese Journal of Antibiotics

基　　金：微生物药物技术创新与新药创制产学研联盟(No.2010ZX09401-403)

摘　　要：目的对四羟基环孢菌素衍生物([γ-HyMeLeu4]CyA)转化菌Nonomuraea dietziae的发酵条件进行优化。方法采用均匀设计对发酵培养基进行优化,考察糊精、黄豆饼粉、葡萄糖、酵母粉和蛋白胨对发酵单位的影响,同时对底物环孢菌素A的添加时间、添加量和发酵培养时间进行了摸索。结果得到了最优培养基配方为:糊精1.2%、葡萄糖3.0%、酵母粉0.9%、蛋白胨0.5%、黄豆饼粉1.5%;底物添加最佳时间是36h,添加量是400μg/mL,最佳放瓶时间是96h。在优化后的培养条件下,[γ-HyMeLeu4]CyA的产量提高了63%左右。结论优化后的发酵条件更适合转化菌的生长,有利于目的产物产量的提高,该发酵条件的优化为[γ-HyMeLeu4]CyA的工业化生产奠定了基础。Objective To optimize fermentation conditions Nonomuraea dietziae. Methods Uniform design method was used to for the production of [γ-HyMeLeu4]CyA by optimize the fermentation medium. The effects of dextrin, soy bean meal, glucose, yeast extract and peptone for the fermentation unit were validated. At the same time, the best substrate adding time, adding dose and the incubation time were investigated in. Results The optimal medium contains 1.2% dextrin, 3.0% glucose, 0.9% yeast extract, 0.5% peptone and 1.5% soy bean meal. The best substrate adding time was 36h, adding dose was 400μg/mL and the incubation time was 96h. Under the optimum condition, the potency of [γ-HyMeLeu4]CyA was 63% higher than that in the control medium. Conclusion The optimum condition is more suitable for Nonomuraea dietziae, beneficial to the improvement of the objective product yield. It had established the foundation for the potency of [γ-HyMeLeua]CyA on industrial scale.

关 键 词：[γ-HyMeLeu4】CyA 发酵条件优化 均匀设计 

分 类 号：R979.5[医药卫生—药品]