Which properties of metabolic networks can be derived solely from
stoichiometric information about the network's constituent reactions?
Predictive results have been obtained by Flux Balance Analysis (FBA), by
postulating that cells set metabolic fluxes within the allowed stoichiometry so
as to maximize their growth. Here, we generalize this framework to single cell
level using maximum entropy models from statistical physics. We define and
compute, for the core metabolism of Escherichia coli, a joint distribution over
all fluxes that yields the experimentally observed growth rate. This solution,
containing FBA as a limiting case, provides a better match to the measured
fluxes in the wild type and several mutants. We find that E. coli metabolism is
close to, but not at, the optimality assumed by FBA. Moreover, our model makes
a wide range of predictions: (i) on flux variability, its regulation, and flux
correlations across individual cells; (ii) on the relative importance of
stoichiometric constraints vs. growth rate optimization; (iii) on quantitative
scaling relations for singe-cell growth rate distributions. We validate these
scaling predictions using data from individual bacterial cells grown in a
microfluidic device at different sub-inhibitory antibiotic concentrations.
Under mild dynamical assumptions, fluctuation-response relations further
predict the autocorrelation timescale in growth data and growth rate adaptation
times following an environmental perturbation.Comment: 12 pages, 4 figure
