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作 者:田勋 高苹[1,2] 刘英 胡海峰[1,2] TIAN Xun;GAO Ping;LIU ying;HU Haifeng(Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 200040;Sinopharm Health Industry Institute Co.,Ltd.,Shanghai 200437)
机构地区:[1]中国医药工业研究总院上海医药工业研究院,上海200040 [2]国药集团健康产业研究院有限公司,上海201203
出 处:《中国医药工业杂志》2020年第1期63-68,共6页Chinese Journal of Pharmaceuticals
摘 要:以荒漠拟孢囊菌SIPI-HT47为出发菌株,发酵合成奥利万星中间体A82846B。应用紫外和NTG诱变,结合自身抗性及氯化盐耐受筛选,获得1株高产突变株,命名为FH-32-322,发酵效价较出发菌株提高172.5%。通过PB试验、爬坡试验和响应面试验设计优化发酵培养基组成,确定最佳摇瓶发酵配方。在优化后的发酵培养基上,突变株FH-32-322摇瓶发酵效价达到1 013 mg/L,较原工艺提高85.9%。To synthesize compound of A82846 B, a key intermediate of oritavancin, a high producing strain named FH-32-322 was obtained by using UV and NTG mutagenesis based on self-resistance and chloride tolerance from original strain Kibdelosporangium aridum SIPI-HT47. The yielding rate of mutant strain increased 172.5% in fermentation titer compared to SIPI-HT47. After optimized by PB, steepest ascent design, and response surface methodology, the optimum composition of medium for shaking flask fermentation was determined. Under optimized condition, the fermentation titer of A82846 B reached up to 1 013 mg/L of shaking flask fermentation, which was 85.9% higher than that of the original strain.
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