Designing intracellular metabolism for production of target compounds by introducing a heterologous metabolic reaction based on a Synechosystis sp. 6803 genome-scale model

Abstract

Background: Designing optimal intracellular metabolism is essential for using microorganisms to produce useful compounds. Computerized calculations for flux balance analysis utilizing a genome-scale model have been performed for such designs. Many genome-scale models have been developed for different microorganisms. However, optimal designs of intracellular metabolism aimed at producing a useful compound often utilize metabolic reactions of only the host microbial cells. In the present study, we added reactions other than the metabolic reactions with Synechosystis sp. 6803 as a host to its genome-scale model, and constructed a metabolic model of hybrid cells (SyHyMeP) using computerized analysis. Using this model provided a metabolic design that improves the theoretical yield of succinic acid, which is a useful compound. Results: Constructing the SyHyMeP model enabled new metabolic designs for producing useful compounds. In the present study, we developed a metabolic design that allowed for improved theoretical yield in the production of succinic acid during glycogen metabolism by Synechosystis sp. 6803. The theoretical yield of succinic acid production using a genome-scale model of these cells was 1.00 mol/mol-glucose, but use of the SyHyMeP model enabled a metabolic design with which a 33 % increase in theoretical yield is expected due to the introduction of isocitrate lyase, adding activations of endogenous tree reactions via D-glycerate in Synechosystis sp. 6803. Conclusions: The SyHyMeP model developed in this study has provided a new metabolic design that is not restricted only to the metabolic reactions of individual microbial cells. The concept of construction of this model requires only replacement of the genome-scale model of the host microbial cells and can thus be applied to various useful microorganisms for metabolic design to produce compounds.