Impact of the solvent capacity constraint on E. coli metabolism
- Equal contributors
1 The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ 08540, USA
2 Department of Pathology, University of Pittsburgh, Pittsburgh, PA, 15261, USA
3 Instituto de Física, Universidade Federal Fluminense, Rio de Janeiro, 24210, Brazil
4 Machine Learning Department, Carnegie-Mellon University, Pittsburgh, PA, 15217, USA
5 Department of Physics and Center for Complex Networks Research, University of Notre Dame, South Bend, IN 46556, USA
6 SiDMAP, LLC and the UCLA School of Medicine, Los Angeles, CA 90064, USA
7 Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
BMC Systems Biology 2008, 2:7 doi:10.1186/1752-0509-2-7Published: 23 January 2008
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.
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.
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.