COMPARATIVE DETERMINATION OF BIOMASS COMPOSITION IN DIFFERENTIALLY ACTIVE METABOLIC STATES

Abstract

Flux Balance Analysis (FBA) has been successfully applied to facilitate the understanding of cellular metabolism in model organisms. Standard formulations of FBA can be applied to large systems, but the accuracy of predictions may vary significantly depending on environmental conditions, genetic perturbations, or complex unknown regulatory constraints. Here we present an FBA-based approach to infer the biomass compositions that best describe multiple physiological states of a cell. Specifically, we seek to use experimental data (such as flux measurements, or mRNA expression levels) to infer best matching stoichiometrically balanced fluxes and metabolite sinks. Our algorithm is designed to provide predictions based on the comparative analysis of two metabolic states (e. g. wild-type and knockout, or two different time points), so as to be independent from possible arbitrary scaling factors. We test our algorithm using experimental data for metabolic fluxes in wild type and gene deletion strains of E. coli. In addition to demonstrating the capacity of our approach to correctly identify known exchange fluxes and biomass compositions, we analyze E. coli central carbon metabolism to show the changes of metabolic objectives and potential compensation for reducing power due to single enzyme gene deletion in pentose phosphate pathway.