Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
Volume 1858, Issue 4, Pages 276-287Publisher
ELSEVIER
DOI: 10.1016/j.bbabio.2016.12.007
Keywords
Flux balance analysis; Carbon partitioning; Cyanobacteria; Gluconeogenesis-pentose phosphate (PP) pathway; Metabolism; Photorespiration; Nitrogen deprivation; Transcriptomic; Synechococcus 7002
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Funding
- US Department of Energy DOE-EERE [DE-EE0003373]
- AFSOR [FA9550-11-1-0231]
- Direct For Biological Sciences [1515511] Funding Source: National Science Foundation
- Div Of Molecular and Cellular Bioscience [1515511] Funding Source: National Science Foundation
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We have constructed and experimentally tested a comprehensive genome-scale model of photoautotrophic growth, denoted iSyp821, for the cyanobacterium Synechococcus sp. PCC 7002. iSyp821 incorporates a variable biomass objective function (vBOF), in which stoichiometries of the major biomass components vary according to light intensity. The vBOF was constrained to fit the measured cellular carbohydrate/protein content under different light intensities. iSyp821 provides rigorous agreement with experimentally measured cell growth rates and inorganic carbon uptake rates as a function of light intensity. iSyp821 predicts two observed metabolic transitions that occur as light intensity increases: 1) from PSI-cyclic to linear electron flow (greater redox energy), and 2) from carbon allocation as proteins (growth) to carbohydrates (energy storage) mode. iSyp821 predicts photoautotrophic carbon flux into 1) a hybrid gluconeogenesis-pentose phosphate (PP) pathway that produces glycogen by an alternative pathway than conventional gluconeogenesis, and 2) the photorespiration pathway to synthesize the essential amino acid, glycine. Quantitative fluxes through both pathways were verified experimentally by following the kinetics of formation of C-13 metabolites from (CO2)-C-13 fixation. iSyp821 was modified to include changes in gene products (enzymes) from experimentally measured transcriptomic data and applied to estimate changes in concentrations of metabolites arising from nutrient stress. Using this strategy, we found that iSyp821 correctly predicts the observed redistribution pattern of carbon products under nitrogen depletion, including decreased rates of CO2 uptake, amino acid synthesis, and increased rates of glycogen and lipid synthesis. (C) 2016 Published by Elsevier B.V.
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