Genome-Scale Fluxome of Synechococcus elongatus UTEX 2973 Using Transient ¹³C-Labeling Data

Synechococcus elongatus UTEX 2973 (Synechococcus 2973) has the shortest reported doubling time (2.1 h) among cyanobacteria, making it a promising platform for the solar-based production of biochemicals. In this meta-analysis, its intracellular flux distribution was recomputed using genome-scale isotopic nonstationary ¹³C-metabolic flux analysis given the labeling dynamics of 13 metabolites reported in an earlier study. To achieve this, a genome-scale mapping model, namely imSyu593, was constructed using the imSyn617 mapping model for Synechocystis sp. PCC 6803 (Synechocystis 6803) as the starting point encompassing 593 reactions. The flux elucidation revealed nearly complete conversion (greater than 96%) of the assimilated carbon into biomass in Synechococcus 2973. In contrast, Synechocystis 6803 achieves complete conversion of only 86% of the assimilated carbon. This high biomass yield was enabled by the reincorporation of the fixed carbons lost in anabolic and photorespiratory pathways in conjunction with flux rerouting through a nondecarboxylating reaction such as phosphoketolase. This reincorporation of lost CO₂ sustains a higher flux through the photorespiratory C2 cycle that fully meets the glycine and serine demands for growth. In accordance with the high carbon efficiency drive, acetyl-coenzyme A was entirely produced using the carbon-efficient phosphoketolase pathway. Comparison of the Synechococcus 2973 flux map with that of Synechocystis 6803 revealed differences in the use of Calvin cycle and photorespiratory pathway reactions. The two species used different reactions for the synthesis of metabolites such as fructose-6-phosphate, glycine, sedoheptulose-7-phosphate, and Ser. These findings allude to a highly carbon-efficient metabolism alongside the fast carbon uptake rate in Synechococcus 2973, which explains its faster growth rate.