Towards a quantitative prediction of the fluxome from the proteome

The promise of proteomics and fluxomics is limited by our current inability to integrate these two levels of cellular organization. Here we present the derivation, experimental parameterization, and appraisal of flux functions that enable the quantitative prediction of changes in metabolic fluxes from changes in enzyme levels. We based our derivation on the hypothesis that, in the determination of steady-state flux changes, the direct proportionality between enzyme concentrations and reaction rates is principal, whereas the complexity of enzyme-metabolite interactions is secondary and can be described using an approximate kinetic format. The quality of the agreement between predicted and experimental fluxes in Lactococcus lactis, supports our hypothesis and demonstrates the need and usefulness of approximative descriptions in the study of complex biological systems. Importantly, these flux functions are scalable to genome-wide networks, and thus drastically expand the capabilities of flux prediction for metabolic engineering efforts beyond those conferred by the currently used constraints-based models.