应用统计学方法设计培养基提高雷帕霉素发酵水平.pdfVIP

  应用统计学方法设计培养基提高雷帕霉素发酵水平 陈晓明 金东伟 余辉 黄捷 程元荣* （福建省微生物研究所，福州 350007 ） 摘要：应用统计学方法设计培养基提高吸水链霉菌FC904-33 发酵合成雷帕霉素水平。首先利用 Plackett-Burman 设计法分析出培养基中影响雷帕霉素发酵水平的四个主要因素：玉米淀粉、葡萄糖、 黄豆饼粉和蛋白胨；其次以 Box-Behnken 设计法及响应面分析法确定了主要因素的最佳浓度：玉米 淀粉 37.25g/L，葡萄糖 5.97g/L，黄豆饼粉29.54g/L ，蛋白胨4.56g/L 。采用优化后培养基进行雷帕霉 素发酵，发酵水平较原培养基提高了 27%，达到预期效果。 关键词：雷帕霉素；Plackett-Burman 设计；Box-Behnken 设计；响应面法；发酵培养基 Statistical experimental methods to design medium applied for improving the titer of rapamycin fermentation * Chen Xiao-ming，Jing Dong-wei ，Yu Hui, Huang Jie and Chen Yuan-rong （FuJian Institute of Microbiology ，Fuzhou 350007 ） Abstract Statistical experimental methods for designing fermentation medium were applied for improving the titer of rapamycin production by Streptomyces hygroscopicus FC904-33. In the first step of optimization, four nutritional factors that influenced the titer of rapamycin most significantly were screened out by Plackett-Burman experimental design ，then optimized by Box-Behnken factorial design and response surface methodology ．The maximum rapamycin titer was predicted in the medium containing cornstarch 37.25g/L, glucose 5.97g/L，soybean cake powder 29.54g/L and peptone 4.56 g/L. Compared to the original medium ，the titer of rapamycin in the optimized medium were increased by 27% ． Key words Rapamycin; titer; Plackett-Burman design; Box-Behnken design; Response surface methodology [1] [2-4] 自雷帕霉素作为器官移植抗排斥药物 ，特别是mTOR靶位的发现及雷帕霉素衍生物 作为 mTOR靶向抗癌药物的研发，这类药物越来越受到人们的重视。为提高雷帕霉素产生菌吸水链霉菌 FC904-33[5-6]发酵合成雷帕霉素的能力，我们尝试应用统计学方法优化高产突变株FC904-33 的发酵培 养基。