响应曲面法优化柔红霉素发酵培养基

Improving the fermentation yield of daunorubicin by response surface analysis

目的优化培养基,提高柔红霉素发酵效价。方法采用Plackett-Burman法、最陡爬坡试验和Box-Behnken设计,用摇瓶发酵进行实验,利用SAS软件进行二次回归分析。结果 Plackett-Burman设计证明麸质粉(A)、FeSO4·7H2O(B)和NaCl(C)对产量影响较大,通过最陡爬坡试验和响应曲面法得到柔红霉素发酵培养基预测模型为:Y=-16.09+13.55A+231.49B+5.20C-3.59A2+130.00AB-30774B2-0.37AC+102.50BC-1.84C2,从中获得柔红霉素发酵的最优配方为:麸质粉2.0%,FeSO4·7H2O 0.01%,NaCl 1.51%。1500L发酵罐中试放大结果表明:柔红霉素效价提高24%。结论使用响应曲面法可以较大幅度地提高柔红霉素发酵效价。

Objective To optimize the culture medium and improve the yield of daunorubicin fermentation. Methods Plackett-Burman designed for the most influencing factors detemination, the path of steepest ascent for the center test point determination, the Box-Behnken designed for the response surface analysis, experimented by shaking flask for fermentation. SAS software for analysis. Results The three factors that selected by Plackett-Burman method were zein（A）, FeSO4·7HEO（B） and NaCI（C）. The result show that the mathematical modal for daunorubicin production is： Y= -16.09＋13.55A＋231.49B＋5.20C-3.59AE＋130.OOAB -30774B2 -0.37AC＋102.50BC-1.84C2. Based on the models, the optimum medium for daunorubicin production is zein 2.0%, FeSO4.7H20 0.01%, NaCl 1.51%, Improved the daunorubicin production in 1500L pilot fermentor by 24%. Conclusion Response surface analysis is able to overcome some drawbacks of the single factor experiment, and can use less experiment times on the experiment conducted a comprehensive study. Response surface analysis is a good combination for improving daunorubicin fermentation yield.