Detecting the Escherichia coli metabolic backbone

Abstract

The heterogeneity of reaction fluxes present in a metabolic network within a single flux state can be exploited to construct the so-called backbone as a reduced version of metabolism. The backbone maintains all significant fluxes producing or consuming metabolites while displaying a substantially decreased number of interconnections and, hence, it becomes a useful tool to extract primary metabolic routes. Here, we disclose the metabolic backbone of Escherichia coli using the computationally predicted fluxes which maximize the growth rate in glucose minimal medium, and we compare it with the backbone of Mycoplasma pneumoniae, a much simpler organism. We find that the central core in both backbones is mainly composed of reactions in ancient pathways, still playing at present a key role in energy metabolism. In E. coli, the analysis of the backbone reveals that the synthesis of nucleotides and the metabolism of lipids form smaller cores which rely critically on energy metabolism; but not conversely. At the same time, an analysis of the dependence of this backbone on media composition leads to the identification of pathways sensitive to environmental changes. The metabolic backbone of an organism is thus useful to trace simultaneously both its evolution and adaptation fingerprints.