An example network featuring the difference in predicted flux distributions between FBA and MD-FBA. Thick arrows represent metabolic reactions and circular nodes represent metabolites. Narrow arrows represent the growth-associated dilution of their attached metabolites. Note that the stoichiometric coefficients for reaction v2 are two molecules of A per one molecule of D. v1 and v6 represent the uptake for metabolites A and X, respectively. B is the sole metabolite within the biomass, and hence the flux through v5 represents the growth rate. Blue (dash-dot) and red (solid) arrows represent reactions predicted to be active by MD-FBA and FBA, respectively, while black (dashed) arrows represent all other reactions. The figure illustrates growth on two media: (a) growth on a medium in which both A and X are present; (b) growth on a medium including only metabolite A. FBA predicts the same growth rate, which is equal to v1 under both media, while MD-FBA predicts a growth rate equal to v1 when both A and X are present in the medium and a growth rate equal to 0.5v1 when only A is included in the medium. The latter is due to the fact that when X is absent from the growth medium, MD-FBA cannot activate reactions v4 and v8, since the dilution of metabolites C and C* cannot be satisfied under this medium. The different flux distributions predicted by the two methods lead to different predictions of enzyme essentiality, as detailed in the main text.
Benyamini et al. Genome Biology 2010 11:R43 doi:10.1186/gb-2010-11-4-r43