Abstract
The present study attempted a computer simulation of the metabolism of a model cyanobacteria, Synechocystis sp. PCC 6803 (PCC 6803) to predict allosteric inhibitions that are likely to occur in photoautotrophic and mixotrophic conditions as well as in a metabolically engineered strain. PCC 6803 is a promising host for direct biochemical production from CO2; however, further investigation of allosteric regulation is required for rational metabolic engineering to produce target compounds. Herein, ensemble modeling of microbial metabolism was applied to build accurate predictive models by synthesizing the results of multiple models with different parameter sets into a single score to identify plausible allosteric inhibitions. The data driven-computer simulation using metabolic flux, enzyme abundance, and metabolite concentration data successfully identified candidates for allosteric inhibition. The enzyme assay experiment using the recombinant protein confirmed isocitrate was a non-competitive inhibitor of phosphoribulokinase as a novel allosteric regulation of cyanobacteria metabolism.