A Genome-Scale Metabolic Model Accurately Predicts Fluxes in Central Carbon Metabolism under Stress Conditions

Thomas C.R. Williams, Mark G. Poolman, Andrew J.M. Howden, Markus Schwarzlander, David A. Fell, R. George Ratcliffe, Lee J. Sweetlove (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)
12 Downloads (Pure)

Abstract

Flux is a key measure of the metabolic phenotype. Recently, complete (genome-scale) metabolic network models have been established for Arabidopsis (Arabidopsis thaliana), and flux distributions have been predicted using constraints-based modeling and optimization algorithms such as linear programming. While these models are useful for investigating possible flux states under different metabolic scenarios, it is not clear how close the predicted flux distributions are to those occurring in vivo. To address this, fluxes were predicted for heterotrophic Arabidopsis cells and compared with fluxes estimated in parallel by 13C-metabolic flux analysis (MFA). Reactions of the central carbon metabolic network (glycolysis, the oxidative pentose phosphate pathway, and the tricarboxylic acid [TCA] cycle) were independently analyzed by the two approaches. Net fluxes in glycolysis and the TCA cycle were predicted accurately from the genome-scale model, whereas the oxidative pentose phosphate pathway was poorly predicted. MFA showed that increased temperature and hyperosmotic stress, which altered cell growth, also affected the intracellular flux distribution. Under both conditions, the genome-scale model was able to predict both the direction and magnitude of the changes in flux: namely, increased TCA cycle and decreased phosphoenolpyruvate carboxylase flux at high temperature and a general decrease in fluxes under hyperosmotic stress. MFA also revealed a 3-fold reduction in carbon-use efficiency at the higher temperature. It is concluded that constraints-based genome-scale modeling can be used to predict flux changes in central carbon metabolism under stress conditions.

Original languageEnglish
Pages (from-to)311-323
Number of pages13
JournalPlant Physiology
Volume154
Issue number1
Early online date6 Jul 2010
DOIs
Publication statusPublished - Sept 2010

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Plant Science

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