Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load

Naama Tepper, Elad Noor, Daniel Amador-Noguez, Hulda S. Haraldsdóttir, Ron Milo, Joshua D. Rabinowitz, Wolfram Liebermeister, Tomer Shlomi

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Steady-state metabolite concentrations in a microorganism typically span several orders of magnitude. The underlying principles governing these concentrations remain poorly understood. Here, we hypothesize that observed variation can be explained in terms of a compromise between factors that favor minimizing metabolite pool sizes (e.g. limited solvent capacity) and the need to effectively utilize existing enzymes. The latter requires adequate thermodynamic driving force in metabolic reactions so that forward flux substantially exceeds reverse flux. To test this hypothesis, we developed a method, metabolic tug-of-war (mTOW), which computes steady-state metabolite concentrations in microorganisms on a genome-scale. mTOW is shown to explain up to 55% of the observed variation in measured metabolite concentrations in E. coli and C. acetobutylicum across various growth media. Our approach, based strictly on first thermodynamic principles, is the first method that successfully predicts high-throughput metabolite concentration data in bacteria across conditions.

Original languageEnglish (US)
Article numbere75370
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 26 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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