Functional analysis of metabolism: a global approach unravels fluxes and protein allocation in E. coli

The complexity of the metabolic networks supporting the cellular production of energy and biomass represents a challenge to the genome-scale analysis of fluxes and proteome allocation. We developed a novel framework that allows to disentangle flux and proteome components associated with the production of energy and of individual biosynthetic precursors. After integrating genome-scale models of metabolism for Escherichia coli with experimental data on fluxes and cellular composition across conditions, we assigned experimental protein abundances to function-specific protein shares, thus quantifying the protein burden associated with each metabolic activity. This approach provides the basis for a function-based coarse graining of the cellular proteome and leads to the formulation of predictive models of protein allocation.