土霉素高产菌株N56育种及工业发酵条件优化  

Breeding and Optimization of Fermentation Conditions for Oxytetracycline Producing Strain N56

作　　者：刘俊芳 张明玉 郑红娜[2] 

机构地区：[1]赤峰制药股份有限公司,内蒙古赤峰024001 [2]内蒙古工业大学化工学院,呼和浩特010051

出　　处：《国外医药（抗生素分册）》2015年第3期117-120,共4页World Notes on Antibiotics

摘　　要：目的以五氟尿嘧啶与紫外线复合氯化锂诱变土霉素产生菌,得到高产突变株。方法以龟裂链霉菌(Streptomyces rimosus)M-24#为出发菌,采用不同工作浓度的五氟尿嘧啶与不同处理时间的紫外线复合氯化锂处理该菌株,经过琼脂块抑菌圈初筛、摇瓶筛选和罐上试验,得到生产性状优良的菌株。结果经过诱变及各步筛选后,获得3株高产菌株,并根据培养特性对它们进行发酵条件的优化,选出经济高效菌株199#,经过自然分离得到高产稳定的菌株N56,在生产车间进行四批30吨罐发酵的研究,发酵水平提高8.75%,同时节约了无菌空气量11.1%。结论五氟尿嘧啶与紫外线复合氯化锂诱变土霉素产生菌效果显著,所获得的高产菌株效价高、需氧量低,节约了大量无菌空气,降低了生产成本。Objective To obtain oxytetracycline high-producing mutant strain by treatmem of fluorouracil, UV irradiation combined with LiC1. Methods Streptomyces rimosus M-24 # was treated with different doses of fluorouracil, UV irradiation combined with LiC1. The regenerated single colonies were first evaluated by inhibition zone on agar, then inoculated in shake flask for the preliminary and secondary selection program for high-yielding stains. Finally, the mutant strain was verified in the 30 tons fermentation tank conditions. Results Three high-yield mutant strains were obtained and their fermentation conditions were optimized according their culture cultivation. Among them, strain 199 was economic and efficient, its natural separation colony strain N56 showed characteristics of high-yielding and genetic stability. Moreover, its average titer increased 8.7% higher than the original strain based on the 4 batches 30 tons tank fermentation, while, saved the aseptic air volume by 11.1% at the same time. Conclusions The breeding method of fluorouracil, UV irradiation combined with LiC1 to kasugamycin-producing strain was efficient. The target strain was suitable to industrial manufacture with the characteristics of high titer and low oxygen consumption, which can reduce the production cost.

关 键 词：土霉素 龟裂链霉菌 诱变育种 发酵 

分 类 号：R978.14[医药卫生—药品]