Systematic analysis of conservation relations in E. coli genome-scale metabolic network reveals novel growth media

¹ University of Pennsylvania School of Medicine
² Boston University
³ University of Pennsylvania

^* To whom correspondence should be addressed. E-mail: imielins{at}mail.med.upenn.edu.

Submitted on June 22, 2005
Revised on August 3, 2005
Accepted on 12 December 2005

	Abstract

A biochemical species is called producible in a constraints-based metabolic model if there exists a feasible steady state flux configuration that sustains its nonzero concentration during growth. Extreme semipositive conservation relations (ESCR) are the simplest semipositive linear combinations of species concentrations that are invariant to all metabolic flux configurations. In this paper, we outline a fundamental relationship between the ESCR of a metabolic network and the producibility of a biochemical species under a nutrient media. We exploit this relationship in an algorithm that systematically enumerates all minimal nutrient sets that render an objective species weakly producible (i.e. producible in the absence of thermodynamic constraints) through a simple traversal of ESCR. We apply our results to a recent genome scale model of E. coli metabolism, in which we traverse the 51 anhydrous ESCR of the metabolic network to determine all 928 minimal aqueous nutrient media that render biomass weakly producible. Applying irreversibility constraints, we find 287 of these 928 nutrient sets to be thermodynamically feasible. We also find that an additional 365 of these nutrient sets are thermodynamically feasible in the presence of oxygen. Since biomass producibility is commonly used as a surrogate for growth in genome scale metabolic models, our results represent testable hypotheses of alternate growth media derived from in silico analysis of the E. coli genome scale metabolic network.

Key Words: E. coli metabolism, conservation relations, genome scale metabolic analysis, metabolite producibility.