Impact of the solvent capacity constraint on E. coli metabolism.
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.


CONCLUSIONS
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.
Vazquez
Alexei
A
The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ 08540, USA. vazquez@ias.edu
Beg
Qasim K
QK
Demenezes
Marcio A
MA
Ernst
Jason
J
Bar-Joseph
Ziv
Z
Barabási
Albert-László
AL
Boros
László G
LG
Oltvai
Zoltán N
ZN
D048429:Cell Size; D004926:Escherichia coli / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005502:Food; D015964:Gene Expression Regulation, Bacterial; D042541:Intracellular Space / Q000378:metabolism; D008954:Models, Biological; D012997:Solvents
D012997:Solvents