Robustness analysis of the Escherichia coli metabolic network
Robustness analysis of the Escherichia coli metabolic network
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DOI：
10.1021/bp0000712
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发表时间：
2000-11-01
影响因子：
2.9
通讯作者：
Palsson, BO
中科院分区：
文献类型：
--
作者：
Edwards, JS;Palsson, BO
基因组、生物化学和菌株特异性数据可以被组合以定义选定组的单细胞生物体的代谢网络的计算机表示。通量平衡分析和表型相平面已被开发并应用于分析大肠杆菌K-12的代谢能力和特征。这些分析表明，在葡萄糖基本培养基中生长的中心代谢途径（糖酵解，戊糖磷酸途径，三羧酸循环）中存在七个基本反应。相应的7个基因产物可以分为三类：（1）戊糖磷酸途径基因，（2）三碳糖酵解基因，和（3）三羧酸循环基因。在这里，我们开发了一个程序，计算最佳的细胞生长的敏感性，改变这些必需的基因产物的通量水平。结果表明，E.大肠杆菌代谢网络是强大的，相对于这些酶的通量水平。转酮醇酶和三羧酸循环反应中的代谢通量可以分别降低到最佳值的15%和19%，而不会显著影响最佳生长通量。代谢网络也表现出相对于核糖-5-磷酸异构酶的鲁棒性，核糖-5-磷酸异构酶通量降低到最佳值的28%，而不显着影响最佳生长通量。代谢网络对三碳糖酵解通量的增加和减少表现出有限的鲁棒性。这一发展为使用FBA研究代谢网络的能力提供了另一个维度。
Genomic, biochemical, and strain-specific data can be assembled to define an in silico representation of the metabolic network for a select group of single cellular organisms. Flux-balance analysis and phenotypic phase planes derived therefrom have been developed and applied to analyze the metabolic capabilities and characteristics of Escherichia coli K-12. These analyses have shown the existence of seven essential reactions in the central metabolic pathways (glycolysis, pentose phosphate pathway, tricarboxylic acid cycle) for the growth in glucose minimal media. The corresponding seven gene products can be grouped into three categories: (1) pentose phosphate pathway genes, (2) three-carbon glycolytic genes, and (3) tricarboxylic acid cycle genes. Here we develop a procedure that calculates the sensitivity of optimal cellular growth to altered flux levels of these essential gene products. The results indicate that the E. coli metabolic network is robust with respect to the flux levels of these enzymes. The metabolic flux in the transketolase and the tricarboxylic acid cycle reactions can be reduced to 15% and 19%, respectively, of the optimal value without significantly influencing the optimal growth flux. The metabolic network also exhibited robustness with respect to the ribose-5-phosphate isomerase, and the ribose-5-phosephate isomerase flux was reduced to 28% of the optimal value without significantly effecting the optimal growth flux. The metabolic network exhibited limited robustness to the three-carbon glycolytic fluxes both increased and decreased. The development presented another dimension to the use of FBA to study the capabilities of metabolic networks.