Multidimensional Optimality of Microbial Metabolism

Although the network topology of metabolism is well known, understanding the principles that govern the distribution of fluxes through metabolism lags behind. Experimentally, these fluxes can be measured by 13C-flux analysis, and there has been a long-standing interest in understanding this functional network operation from an evolutionary perspective. On the basis of 13C-determined fluxes from nine bacteria and multi-objective optimization theory, we show that metabolism operates close to the Pareto-optimal surface of a three-dimensional space defined by competing objectives. Consistent with flux data from evolved Escherichia coli, we propose that flux states evolve under the trade-off between two principles: optimality under one given condition and minimal adjustment between conditions. These principles form the forces by which evolution shapes metabolic fluxes in microorganisms’ environmental context.