Multidimensional optimality of microbial metabolism

Science. 2012 May 4;336(6081):601-4. doi: 10.1126/science.1216882.


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 (13)C-flux analysis, and there has been a long-standing interest in understanding this functional network operation from an evolutionary perspective. On the basis of (13)C-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Adenosine Triphosphate / metabolism
  • Aerobiosis
  • Algorithms
  • Bacteria / growth & development
  • Bacteria / metabolism*
  • Biological Evolution*
  • Biomass
  • Computer Simulation
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism*
  • Glucose / metabolism
  • Metabolic Networks and Pathways*
  • Models, Biological


  • Adenosine Triphosphate
  • Glucose