大肠杆菌苏氨酸合成途径动力学模型的构建与分析

Development and analysis of a kinetic model for Escherichia coli threonine biosynthesis

摘要:

动力学模型分析有利于理解生物系统的调控机制，从而为高效细胞工厂的理性设计提供指导。基于以往发表的相关途径动力学模型和测量的酶动力学数据，开发了大肠杆菌苏氨酸合成途径的动力学模型。模型包含从天冬氨酸至苏氨酸的合成途径及葡萄糖开始的为合成途径提供前体以及能量的代谢途径。与以往模型不同的是新模型中考虑了能量和还原力的平衡，从而使模型模拟的系统自身成为一个不需要从外界提供能量和还原力的自洽系统。模型稳态分析的结果表明PTS、G6PDH和HDH等反应对苏氨酸合成反应的通量控制系数较大，通过过表达这些反应的酶可以有效增加苏氨酸合成反应的通量。

Abstract:

Kinetic model analysis is a useful tool for understanding the regulation and control of cellular metabolism and thus offering a guideline for rational design of high efficiency cell factory. Based on previously published models and experimental measurement of enzyme kinetics data, we developed a kinetic model for the threonine biosynthesis pathway in Escherichia coli. This model integrates the central pathways that produce precursors, ATP and reducing power with the threonine biosynthesis pathway from aspartate. In contrast to the previous models, we considered the energy and reducing power balance rather than artificially set their concentrations. Metabolic control analysis of the model showed that enzymes PTS, G6PDH, HDH etc. have great flux control coefficients on the threonine biosynthesis flux. This indicates higher threonine synthesis flux could be achieved by overexpressing these enzymes.