文献类型：期刊文献

中文题名：去甲金霉素发酵培养基的优化及机制分析

英文题名：Optimization of Fermentation Medium of Demethylchlortetracycline and Mechanism Analysis

作者：李士杭[1];叶蕊芳[1];吕和平[2];毛全贵[2];戴维[2]

机构：[1]华东理工大学生物反应器工程国家重点实验室,上海200237;[2]河南天方药业股份有限公司,河南驻马店463000

年份：2012

卷号：43

期号：11

起止页码：896

中文期刊名：中国医药工业杂志

外文期刊名：Chinese Journal of Pharmaceuticals

收录：CSTPCD;;北大核心:【北大核心2011】；CSCD:【CSCD2011_2012】；

语种：中文

中文关键词：去甲金霉素;发酵;培养基优化

外文关键词：demethylchlortetracycline; fermentation; medium optimization

摘要：以金色链霉菌发酵制备去甲金霉素(1),优化其培养基组成。通过Minitab软件设计Plackett-Burman试验筛选出玉米淀粉、黄豆粉和碳酸钙这3个对1发酵效价影响较大的因素,继而通过最陡爬坡试验和响应面优化确定3个因素的最佳水平:玉米淀粉110 g/L、黄豆粉43 g/L、碳酸钙7 g/L。培养基优化后,1的发酵效价提高了25%～31%。比较优化前后培养基的碳氮比并进行氨基酸添加试验,结果提示1效价的提高可能是多种因素协同作用所致。分析了优化前后发酵过程中相关有机酸和CoA羧基转移酶比活力的变化趋势,结果显示培养基优化后,在发酵中期胞外积累了大量的草酰乙酸和丙二酸,后期进入细胞以合成产物,酶比活力的变化趋势与丙二酸及1效价的变化趋势吻合。
Demethylchlortetracycline （1） was prepared from Streptomyces aureus. The components of the culture medium were optimized. Three important ingredients which influenced the potency obviously in fermentation medium were found by Plackett-Burman experiment through Minitab software and they were corn starch, soybean meal and CaCO3. The optimal concentrations of the three ingredients were determined by steepest ascent search and response surface optimization. The results revealed that the potency was 25% -31% higher than the initial fermentation medium at corn starch of 110 g/L, soybean meal of 43 g/L and CaCO3 of 7 g/L. The experiments about changing C/N and adding amino acids indicated that the potency increase was possibly caused by many factors. After the analysis of the related organic acids and CoA carboxyl transferase, the results indicated that more extracellular oxaloacetic acid and malonic acid were accumulated in the optimized medium in the middle phase. Both of them entered into the cells at the end of fermentation and the demethylchlortetracycline was synthesized greatly. The results also indicated the trend of enzymatic specific activity was anastomotic with that of malonic acid and the potency.