响应面法优化青霉素发酵培养基

Optimization of Penicillin Fermentation Medium by Response Surface Methodology

以产黄青霉(Penicillium chrysogenum)PC-01为生产菌株,利用响应面法优化了青霉素合成的原始摇瓶发酵培养基配方。对原始发酵培养基中的6个成分进行析因试验,采用Minitab16软件分析显示玉米浆、乳糖和磷酸二氢钾这3个因素对青霉素发酵影响显著;将其他3个影响不显著的因子固定在适当水平,对上述3个显著影响因子进行最陡爬坡试验,确定了最优条件范围;再利用中心组合试验确定了最优条件。优化后的培养基配方为:玉米浆15.9 g/L、乳糖104.8 g/L、磷酸二氢钾5.5 g/L、硫酸铵2.5 g/L、硫酸钠0.5 g/L和碳酸钙5 g/L。在此条件下,青霉素的理论产量为16 996 u/ml,经验证,实际产量(17 101 u/ml)与预计产量相差0.62%,较初始青霉素产量(12 500 u/ml)提高了36.8%,降低了杂质组分的含量。

The original penicillin fermentation medium was optimized by response surface methodology with Penicillium chrysogenum PC-01 as the production strain. Six components of the original fermentation medium were analyzed by the factorial experiment. With the aid of Minitabl6 software analysis, it was found that corn steep liquor, lactose and potassium dihydrogen phosphate were three factors affecting penicillin fermentation significantly. Then the steepest ascent experiment was carried out by varying the three significant factors and fixing the three insignificant factors at an appropriate level, and thus the range of the optimal condition was determined. Finally, the central composite design was employed to determine the optimal condition. The optimized recipe of the medium was as follows： com steep liquor 15.9 g/L, lactose 104.8 g/L, potassium dihydrogen phosphate 5.5 g/L, ammonium sulfate 2.5 g/L, sodium sulfate 0.5 g/L and calcium carbonate 5 g/L. Under this condition, the predicted yield of penicillin was 16 996 u/ml. The verifying experiment proved that the difference between the actual yield （17 101 u/ml） and the predicted yield was only 0.62 %. The yield was increased by 36.8 % compared with the initial production （12 500 u/ml）. The impurity content was reduced.