Research article

Impact of the solvent capacity constraint on E. coli metabolism

Alexei Vazquez^{* 1} , Qasim K Beg^{* 2,7} , Marcio A deMenezes³ , Jason Ernst⁴ , Ziv Bar-Joseph⁴ , Albert-László Barabási⁵ , László G Boros⁶ and Zoltán N Oltvai²

¹The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ 08540, USA

²Department of Pathology, University of Pittsburgh, Pittsburgh, PA, 15261, USA

³Instituto de Física, Universidade Federal Fluminense, Rio de Janeiro, 24210, Brazil

⁴Machine Learning Department, Carnegie-Mellon University, Pittsburgh, PA, 15217, USA

⁵Department of Physics and Center for Complex Networks Research, University of Notre Dame, South Bend, IN 46556, USA

⁶SiDMAP, LLC and the UCLA School of Medicine, Los Angeles, CA 90064, USA

⁷Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA

author email corresponding author email* Contributed equally

BMC Systems Biology 2008, 2:7doi:10.1186/1752-0509-2-7

Published:	23 January 2008

Abstract

Background

Obtaining quantitative predictions for cellular metabolic activities requires the identification and modeling of the physicochemical constraints that are relevant at physiological growth conditions. Molecular crowding in a cell's cytoplasm is one such potential constraint, as it limits the solvent capacity available to metabolic enzymes.

Results

Using a recently introduced flux balance modeling framework (FBAwMC) here we demonstrate that this constraint determines a metabolic switch in E. coli cells when they are shifted from low to high growth rates. The switch is characterized by a change in effective optimization strategy, the excretion of acetate at high growth rates, and a global reorganization of E. coli metabolic fluxes, the latter being partially confirmed by flux measurements of central metabolic reactions.

Conclusion

These results implicate the solvent capacity as an important physiological constraint acting on E. coli cells operating at high metabolic rates and for the activation of a metabolic switch when they are shifted from low to high growth rates. The relevance of this constraint in the context of both the aerobic ethanol excretion seen in fast growing yeast cells (Crabtree effect) and the aerobic glycolysis observed in rapidly dividing cancer cells (Warburg effect) should be addressed in the future.