Genome-Scale Flux Elucidation in the Fast-Growing Cyanobacterium Synechococcus Elongatus Utex 2973

Hendry, J. I., The Pennsylvania State University
Maranas, C. D., The Pennsylvania State University
Gopalakrishnan, S., The Pennsylvania State University
Pakrasi, H. B., Washington University
Tang, Y. J., Washington University
A short doubling time of 2h makes Synechococcus elongatus UTEX 2973 a promising platform for solar based production of biofuels and other bio-chemicals. Successful metabolic engineering strategies can be informed by the knowledge of intracellular flux distribution in this organism. In this meta-analysis, the intracellular flux distribution in a genome-scale metabolic model of Synechococcus elongatus UTEX 2973 was elucidated using isotopic non-stationary 13C-metabolic flux analysis using the experimentally measured labeling dynamics of 13 central carbon metabolites reported in an earlier study. To this end, a genome scale carbon mapping model, imSyu593, was constructed using the existing mapping model for Synechocystis sp PCC 6803, imSyn617, as the starting point to trace the flow of carbons through 593 reactions spreading across the central carbon metabolism, amino acid metabolism and peripheral pathways. Flux elucidation revealed a near complete routing (>96%) of the assimilated carbons to biomass formation. This high biomass yield is afforded by the ability of this organism to reincorporate carbons oxidized in anabolic and photorespiratory pathways while increasing the flux through non-decarboxylating reactions. The ability to reincorporate oxidized carbons sustains a higher flux through the photorespiratory C2 cycle to meet the glycine and serine demand for the biomass synthesis. In contrast with other cyanobacteria, Malic enzyme is found to be dispensable with pyruvate being synthesized via Pyruvate Kinase. And instead of using the lower glycolysis and Pyruvate Dehydrogenase reaction, Acetyl-CoA was synthesized using the carbon efficient Phosphoketolase pathway. These findings suggest the existence of a highly efficient metabolism in Synechococcus elongatus UTEX 2973, which, in conjunction with fast growth rate, supports the development of this organism into an ideal photoautotrophic production platform.