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Science 336 (6081): 601-604

Copyright © 2012 by the American Association for the Advancement of Science

Multidimensional Optimality of Microbial Metabolism

Robert Schuetz,1 Nicola Zamboni,1 Mattia Zampieri,1 Matthias Heinemann,1,2 Uwe Sauer1,*

Abstract: 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.

1 Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich, Switzerland.
2 Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands.

* To whom correspondence should be addressed. E-mail: sauer{at}

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