title: Flux balance analysis of photoautotrophic metabolism: Uncovering new biological details of subsystems involved in cyanobacterial photosynthesis.
abstract: 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 of13C metabolites from13CO2fixation. 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 CO2uptake, amino acid synthesis, and increased rates of glycogen and lipid synthesis.
authors.affiliation: Waksman Institute, Rutgers University, New Brunswick, NJ 08901, USA. Electronic address: xiaoqian@waksman.rutgers.edu.
authors.forename: Xiao
authors.initials: X
authors.lastname: Qian
authors.affiliation: Center for Computational and Integrative Biology, Rutgers University, Camden, NJ 08102, USA. Electronic address: mk1034@rutgers.edu.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Center for Computational and Integrative Biology, Rutgers University, Camden, NJ 08102, USA. Electronic address: kumargk@waksman.rutgers.edu.
authors.forename: G Kenchappa
authors.initials: GK
authors.lastname: Kumaraswamy
authors.affiliation: Department of Marine Science, Rutgers University, New Brunswick, NJ 08901, USA. Electronic address: aa1041@scarletmail.rutgers.edu.
authors.forename: Ananya
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Center for Computational and Integrative Biology, Rutgers University, Camden, NJ 08102, USA; Department of Computer Science, Rutgers University, Camden, NJ 08102, USA; Department of Plant Biology and Pathology, Rutgers University, New Brunswick, NJ 08901, USA; School of Information Technology and Mathematical Sciences, University of South Australia, Mawson Lakes, SA 5095, Australia. Electronic address: dslun@rutgers.edu.
authors.forename: Desmond S
authors.initials: DS
authors.lastname: Lun
authors.affiliation: Waksman Institute, Rutgers University, New Brunswick, NJ 08901, USA; Department of Chemistry& Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: dismukes@rutgers.edu.
authors.forename: G Charles
authors.initials: GC
authors.lastname: Dismukes
mesh_terms: D002244:Carbon / Q000378:metabolism; D057486:Carbon Cycle; D020869:Gene Expression Profiling; D010788:Photosynthesis; D046940:Synechococcus / Q000378:metabolism*
chemical_list: D002244:Carbon
keywords: Carbon partitioning; Cyanobacteria; Flux balance analysis; Gluconeogenesis-pentose phosphate (PP) pathway; Metabolism; Nitrogen deprivation; Photorespiration; Synechococcus 7002; Transcriptomic