Genome-scale metabolic models have proven useful for answering fundamental questions about metabolic capabilities of a variety of microorganisms, as well as informing their metabolic engineering. However, only a few models are available for oxygenic photosynthetic microorganisms, particularly in cyanobacteria in which photosynthetic and respiratory electron transport chains (ETC) share components. We addressed the complexity of cyanobacterial ETC by developing a genome-scale model for the diazotrophic cyanobacterium, Cyanothece sp. ATCC 51142. The resulting metabolic reconstruction, iCce806, consists of 806 genes associated with 667 metabolic reactions and includes a detailed representation of the ETC and a biomass equation based on experimental measurements. Both computational and experimental approaches were used to investigate light-driven metabolism in Cyanothece sp. ATCC 51142, with a particular focus on reductant production and partitioning within the ETC. The simulation results suggest that growth and metabolic flux distributions are substantially impacted by the relative amounts of light going into the individual photosystems. When growth is limited by the flux through photosystem I, terminal respiratory oxidases are predicted to be an important mechanism for removing excess reductant. Similarly, under photosystem II flux limitation, excess electron carriers must be removed via cyclic electron transport. Furthermore, in silico calculations were in good quantitative agreement with the measured growth rates whereas predictions of reaction usage were qualitatively consistent with protein and mRNA expression data, which we used to further improve the resolution of intracellular flux values.
Cyanobacteria have been promoted as platforms for biofuel production due to their useful physiological properties such as photosynthesis, relatively rapid growth rates, ability to accumulate high amounts of intracellular compounds and tolerance to extreme environments. However, development of a computational model is an important step to synthesize biochemical, physiological and regulatory understanding of photoautotrophic metabolism (either qualitatively or quantitatively) at a systems level, to make metabolic engineering of these organisms tractable. When integrated with other genome-scale data ( e.g., expression data), numerical simulations can provide experimentally testable predictions of carbon fluxes and reductant partitioning to different biosynthetic pathways and macromolecular synthesis. This work is the first to computationally explore the interactions between components of photosynthetic and respiratory systems in detail. In silico predictions obtained from model analysis provided insights into the effects of light quantity and quality upon fluxes through electron transport pathways, alternative pathways for reductant consumption and carbon metabolism. The model will not only serve as a platform to develop genome-scale metabolic models for other cyanobacteria, but also as an engineering tool for manipulation of photosynthetic microorganisms to improve biofuel production.