Mathematical study of feedback inhibition effects on the dynamics of metabolites on the central metabolism of a yeast cell: a combination of kinetic model and metabolic control analysis

Abstract

The fermentation system is a metabolic system that can be considered as a complex system, since it involves metabolites linked by different reactions. Some outputs of the reaction act as input in the other reactions and they control the behaviour of the system. Glucose as the main carbon source of the yeast cells plays an important role in the cell's reproduction cycle and product synthesis. Glucose promotes negative feedback to some reactions in the central metabolism of the yeast cell. In this paper we mathematically study the effects of the negative feedback (inhibition) by glucose and other metabolites on the dynamics of the fermentation system. We also study the sensitivity of the flux in the presence of inhibition. We found that high inhibition by glucose affects the concentration of acetyl-CoA, which will lead to the respiration pathway of the yeast cells. High inhibition by acetaldehyde affects the concentration of all metabolites, including the maximal concentration of ethanol. Based on the metabolic control analysis results, we found that glucose can be considered as the external regulating point in increasing the flux of ethanol. Although glucose acts as a negative feedback, it can also be used to promote certain processes in the metabolic pathway since it gives the highest positive control in increasing the flux of ethanol as the desired product. For the internal regulation point, the maximal concentration of ethanol can be increased significantly by regulating the maximal activity of alcohol dehydrogenase and acetaldehyde dehydrogenase simultaneously.

A numerical study of the sensitivity of ethanol flux to the existence of co-factors in the Central metabolism of a yeast cell using multi-substrate enzymes kinetic modelling

“…As seen in Figure 1, the carbon metabolism of the yeast cell is started with the transport of glucose across the cell membrane through facilitated diffusion [34][35][36][37][38]. The transport process is modelled as [34]:…”

“…As a cellular metabolism with beneficial products, fermentation has been intensively studied by many researchers to find its optimal performances [23][24][25][26][27][28][29]. Some studies were performed in term of theoretical studies using modelling approach [23,24,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] with Saccharomyces cerevisiae as the most studied fermentation microorganism. Some aspects were focused to study such as investigation of glucose transport, understanding the glycolysis process, probability the appearance of oscillatory behaviour in the yeast glycolytic, study the effect of dilution rate to the dynamic of metabolites, etc.…”