Genome-Scale Metabolic Network Reconstruction and In Silico Analysis of Hexanoic acid Producing Megasphaera elsdenii

摘要

Hexanoic acid and its derivatives have been recently recognized as value-added materials and can be synthesized by several microbes. Of them, has been considered as an interesting hexanoic acid producer because of its capability to utilize a variety of carbons sources. However, the cellular metabolism and physiology of still remain uncharacterized. Therefore, in order to better understand hexanoic acid synthetic metabolism in , we newly reconstructed its genome-scale metabolic model, ME375, which accounts for 375 genes, 521 reactions, and 443 metabolites. A constraint-based analysis was then employed to evaluate cell growth under various conditions. Subsequently, a flux ratio analysis was conducted to understand the mechanism of bifurcated hexanoic acid synthetic pathways, including the typical fatty acid synthetic pathway via acetyl-CoA and the TCA cycle in a counterclockwise direction through succinate. The resultant metabolic states showed that the highest hexanoic acid production could be achieved when the balanced fractional contribution via acetyl-CoA and succinate in reductive TCA cycle was formed in various cell growth rates. The highest hexanoic acid production was maintained in the most perturbed flux ratio, as phosphoenolpyruvate carboxykinase ( ) enables the bifurcated pathway to form consistent fluxes. Finally, organic acid consuming simulations suggested that succinate can increase both biomass formation and hexanoic acid production.