Robustness analysis of the Escherichia coli metabolic network

Genomic, biochemical, and strain-specific data can be assembled to define a n in silico representation of the metabolic network for a select group of s ingle 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 metabo lic pathways (glycolysis, pentose phosphate pathway, tricarboxylic acid cyc le) for the growth in glucose minimal media. The corresponding seven gene p roducts 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 opti mal cellular growth to altered flux levels of these essential gene products . The results indicate that the E. coli metabolic network is robust with re spect to the flux levels of these enzymes. The metabolic flux in the transk etolase and the tricarboxylic acid cycle reactions can be reduced to 15% an d 19%, respectively, of the optimal value without significantly influencing the optimal growth flux. The metabolic network also exhibited robustness w ith respect to the ribose-5-phosphate isomerase, and the ribose-5-phosephat e isomerase flux was reduced to 28% of the optimal value without significan tly effecting the optimal growth flux. The metabolic network exhibited limi ted robustness to the three-carbon glycolytic fluxes both increased and dec reased. The development presented another dimension to the use of FBA to st udy the capabilities of metabolic networks.