在模型化基础上对青霉素补料分批发酵过程中经济效益的预测

Modeling-Based Prediction of Economic Performance for Fed-Batch Fermentation Process of Penicillin

在研究发酵动力学、生物过程反应计量学、代谢流分布和代谢流控制的基础上 ,结合专家知识、实验及生产数据 ,对生产规模的青霉素反复补料分批发酵 (即半连续发酵 )的全过程进行了数学模拟 ,建立了一套包含 2 5个过程变量和一系列经济学变量的改良机理模型 .根据这一模型 ,预测了一些工艺参数和经济学参数的改变对发酵过程经济效益的影响 ,发现在保持最大生物质浓度、稀释速率 ,及其它工艺条件不变的情况下 ,中间放料间隔时间、初始发酵液体积以及葡萄糖和电力的价格对经济效益产生较大的影响 .模拟运算结果表明 ,葡萄糖和电力的价格降低 5 % ,全年利润可分别提高 6 .35 %和 3.75 % ;中间放料间隔时间由 2 4h缩短为 12h和 1h(接近于连续发酵 ) ,全年利润可分别提高 7.2 2 %和 14 .11% ;初始发酵液装罐体积分数由 75 %提高到 85 % ,全年发酵利润可提高 5 .4 8% .

An improved mechanical(semi continuous) model including 25 process variables and a series of cost variables was set up for repeated fed batch penicillin fermentation process in an industrial scale bioreactor. The model is based on research of fermentation kinetics and bioprocess stoichiometry, and on analysis of metabolic flux distribution and control, and also combined with expert knowledge and vast amount of experimental and industrial data. With this model, the influence of some process variables and cost variables on economic performance of the fermentation process can be predicted. It was discovered that, the price of glucose and electric power, the initial volume of the broth, and the interval of withdrawing the broth in fermentation process had a great effect upon economic performance , while the maximum biomass concentration, the maximum operation volume, the dilution rate, and other fermentation conditions were kept at same levels. The simulation results show that, the price of glucose and electric power drops 5%, the profit of penicillin fermentation per year would increase 6.36% and 3.75%, respectively; if the initial volume of the broth is increased to 85% of maximum operation volume from 75%, the profit per year would increase 5.48%; and when the interval of withdrawing the broth is shortened from 24 h to 12 h and 1 h(which is almost a continuous fermentation ), the profit per year would increase 7.22% and 14.11%, respectively.