Classification and sensitivity analysis of a proposed primary metabolic reaction network for Streptomyces lividans

Constructing a metabolic flux analysis model is in principle fairly straightforward. However, there are a number of mathematical pitfalls. First, dependent reactions are a recurring problem and, second, the choice of reactions to measure may not be straight-forward. A method for systematic identification of dependent reactions and a thorough reactions classification procedure is presented. A well-defined stoichiometric presentation can provide significant insight into metabolic control mechanisms. Two methods for analyzing the impact of perturbations in the measured fluxes on the remaining metabolism and the impact of changes in biomass composition on the calculated metabolic reactions is developed. A metabolic reaction network proposed for Streptomyces lividans is used as an example to demonstrate the outlined analysis. It is concluded that oxygen utilization has the highest influence on the pathway fluxes and that realistic perturbations in the biomass composition do not significantly alter the flux patterns.