A novel algorithm to calculate elementary modes: Analysis of Campylobacter jejuni metabolism

Abstract

We describe a novel algorithm, ‘LPEM’, that given a steady-state flux vector from a (possibly genome-scale) metabolic model, decomposes that vector into a set of weighted elementary modes such that the sum of these elementary modes is equal to the original flux vector.We apply the algorithm to a genome scale metabolic model of the human pathogen Campylobacter jejuni. This organism is unusual in that it has an absolute growth requirement for oxygen, despite being able to operate the electron transport chain anaerobically.We conclude that (1) Microaerophilly in C. jejuni can be explained by the dependence of pyridoxine 5′-phosphate oxidase for the synthesis of pyridoxal 5′- phosphate (the biologically active form of vitamin B6), (2) The LPEM algorithm is capable of determining the elementary modes of a linear programming solution describing the simultaneous production of 51 biomass precursors, (3) Elementary modes for the production of individual biomass precursors are significantly more complex when all others are produced simultaneously than those for the same product in isolation and (4) The sum of elementary modes for the production of all precursors in isolation requires a greater number of reactions and overall total flux than the simultaneous production of all precursors.