method for accounting for maintenance costs in flux balance analysis improves the prediction of plant cell metabolic phenotypes under stress conditions

• Published in: The Plant journal : for cell and molecular biology 2013-09, Vol.75 (6), p.1050-1061
• Main Authors: Cheung, C. Y. Maurice, Williams, Thomas C. R, Poolman, Mark G, Fell, David. A, Ratcliffe, R. George, Sweetlove, Lee J
• Format: Article
• Language: English
• Subjects: adenosine triphosphate; Adenosine Triphosphate - genetics; Adenosine Triphosphate - metabolism; Arabidopsis; Arabidopsis - enzymology; Arabidopsis - genetics; Arabidopsis - metabolism; Arabidopsis thaliana; Biomass; Biosynthesis; Cell Compartmentation - genetics; cell maintenance; Cells; energy; Energy Metabolism - genetics; flux balance analysis; Genome, Plant; genome‐scale metabolic model; Genotype & phenotype; glycolysis; Hot Temperature; hyper‐osmotic stress; metabolic flux analysis; Metabolism; NADP (coenzyme); NADP - genetics; NADP - metabolism; new methods; Osmotic Pressure; pentose phosphate cycle; Phenotype; Plant biology; prediction; Stress, Physiological - genetics; subcellular compartmentation; technical advance; temperature; temperature stress; transport
• ISSN: 0960-7412; 1365-313X
• DOI: 10.1111/tpj.12252

Flux balance models of metabolism generally utilize synthesis of biomass as the main determinant of intracellular fluxes. However, the biomass constraint alone is not sufficient to predict realistic fluxes in central heterotrophic metabolism of plant cells because of the major demand on the energy budget due to transport costs and cell maintenance. This major limitation can be addressed by incorporating transport steps into the metabolic model and by implementing a procedure that uses Pareto optimality analysis to explore the trade‐off between ATP and NADPH production for maintenance. This leads to a method for predicting cell maintenance costs on the basis of the measured flux ratio between the oxidative steps of the oxidative pentose phosphate pathway and glycolysis. We show that accounting for transport and maintenance costs substantially improves the accuracy of fluxes predicted from a flux balance model of heterotrophic Arabidopsis cells in culture, irrespective of the objective function used in the analysis. Moreover, when the new method was applied to cells under control, elevated temperature and hyper‐osmotic conditions, only elevated temperature led to a substantial increase in cell maintenance costs. It is concluded that the hyper‐osmotic conditions tested did not impose a metabolic stress, in as much as the metabolic network is not forced to devote more resources to cell maintenance.