重组毕氏酵母发酵过程的结构模型

分析了毕氏酵母（Pichia pastoris)以甘油和甲醇为碳源时的代谢途径，建立了胞内物质流和能量流的平衡方程－结构模型。经过适当的降维，解得比碳源消耗速率，比氧消耗速率，比乙酰辅酶A生成速率，细胞比生长速率等关键反应速率。结合反应器模型获得操作变量与过程状态变量间的关系。用实验数据对模型进行了初步验证。结果表明，该模型能较准确地描述细胞生长和重组蛋白合成过程。

Structured Modelling for Recombinant Pichia pastoris

Kinetics of the recombinant Pichia pastoris expressing recombinant human serum albumin (rHSA) was studied. Based on the analysis of metabolic pathways of glycerol and methanol, a structured model describing the balance of intracellular substance and energy flow rates was constructed. After dimension reduction, the key reaction rates such as the specific substrate consumption rate, the specific oxygen uptake rate, the specific acetyl CoA formation rate as well as the specific growth rate were obtained. These reaction rates were then coupled into a bioreactor model so that the relationship between manipulating variables and state variables was set up. Experimental data were used to validate the model. The simulations show that the proposed model may well describe cell growth and rHSA production, which forms the basis for further process optimization.