Intracellular crowding defines the mode and sequence of substrate uptake by Escherichia coli and constrains its metabolic activity

Q. K. Beg, A. Vazquez, J. Ernst, M. A. De Menezes, Z. Bar-Joseph, A. L. Barabási, Z. N. Oltvai

Research output: Contribution to journalArticle

190 Scopus citations

Abstract

The influence of the high intracellular concentration of macromolecules on cell physiology is increasingly appreciated, but its impact on system-level cellular functions remains poorly quantified. To assess its potential effect, here we develop a flux balance model of Escherichia coli cell metabolism that takes into account a systems-level constraint for the concentration of enzymes catalyzing the various metabolic reactions in the crowded cytoplasm. We demonstrate that the model's predictions for the relative maximum growth rate of wild-type and mutant E coli cells in single substrate-limited media, and the sequence and mode of substrate uptake and utilization from a complex medium are in good agreement with subsequent experimental observations. These results suggest that molecular crowding represents a bound on the achievable functional states of a metabolic network, and they indicate that models incorporating this constraint can systematically identify alterations in cellular metabolism activated in response to environmental change.

Original languageEnglish (US)
Pages (from-to)12663-12668
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number31
DOIs
StatePublished - Jul 31 2007

Keywords

  • Flux balance analysis
  • Metabolic networks
  • Systems biology

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