Dynamic modeling of the central carbon metabolism of Escherichia coli
Dynamic modeling of the central carbon metabolism of Escherichia coli
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DOI：
10.1002/bit.10288
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发表时间：
2002-07-05
影响因子：
3.8
通讯作者：
Reuss, M
中科院分区：
文献类型：
--
作者：
Chassagnole, C;Noisommit-Rizzi, N;Reuss, M
应用代谢工程原理合理设计微生物生产过程，关键取决于定量描述中心碳代谢的系统行为，以将碳通量重定向到产物形成途径的能力。尽管几个生产过程的重要性，大肠杆菌的中心碳代谢的一个重要的动态模型的发展已严重阻碍了目前缺乏动力学信息的代谢反应的动力学。在这里，我们提出了这样一个动态模型的设计和实验验证，该模型首次将糖转运系统（即，磷酸转移酶系统[PTS]）与糖酵解和戊糖-磷酸途径的反应。在瞬态条件下的细胞内浓度的代谢物和彗星的实验观察被用来验证模型的结构，并估计动力学参数。系统的详细特性的进一步分析提供了研究代谢通量的稳定性和控制的重要问题的可能性。(C)2002 Wiley Periodicals，Inc.
Application of metabolic engineering principles to the rational design of microbial production processes crucially depends on the ability to describe quantitatively the systemic behavior of the central carbon metabolism to redirect carbon fluxes to the product-forming pathways. Despite the importance for several production processes, development of an essential dynamic model for central carbon metabolism of Escherichia coli has been severely hampered by the current lack of kinetic information on the dynamics of the metabolic reactions. Here we present the design and experimental validation of such a dynamic model, which, for the first time, links the sugar transport system (i.e., phosphotransferase system [PTS]) with the reactions of glycolysis and the pentose-phosphate pathway. Experimental observations of intracellular concentrations of metabolites and cometabolites at transient conditions are used to validate the structure of the model and to estimate the kinetic parameters. Further analysis of the detailed characteristics of the system offers the possibility of studying important questions regarding the stability and control of metabolic fluxes. (C) 2002 Wiley Periodicals, Inc.