用遗传算法进行重组大肠杆菌发酵动力学的分析

Application of Genetic Algorithm to Kinetic Analysis of Recombinant Escherichia Coli Cultivation

重组大肠杆菌在诱导表达人表皮生长因子的过程促使细菌的生长受到抑制,一部分重组菌丧失了分裂能力,但仍保持着一定的代谢活力,分离成为存活但不能培养的细菌,根据大肠杆菌在表达外源蛋白过程中细胞生理状态的不同将细菌分为三类,提出一个描述诱导表达过程中重组大肠杆菌分离、生长的动力学模型．应用遗传算法对不同底物浓度的细胞生长、分离和产物合成的动力学参数进行了有效地估计,避免了传统算法可能陷于局部最优的问题,模型计算结果与实验结果吻合良好．分离模型在初始糖浓为5-20g/L的范围内可以较好地描述发酵过程中细胞生长、分离和目标产物表达的过程并具有一定的预测能力．

The growth inhibition in the human epidermal growth factor expression process is observed. Many recombinant cells segregate into viable but non-culturable cells in the postinduction phase. Depending on the cell ability for cell division and plasmid maintenance, the recombinant cells are grouped into three populations. A segregated kinetic model is proposed to describe the growth and the segregation of the different cell types. Laboratory data from benchscale fermentations involving cell growth, cell segregation and protein production by recombinant Escherichia coli on glucose are investigated. Genetic algorithm is applied to estimate the kinetic parameters and show high estimation precision and better convergence. The segregated kinetic model can be applied to predict the procedure of cell growth, cell segregation and foreign protein production in batch culture of recombinant E.coli within the initial glucose range of 5-20 g/L.