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

Abstract

Metabolic engineering of a yeast fermentation process with an intention of increasing ethanol production is a challenging engineering task since the fermentation system involves multi-enzymes and multi-substrates systems. When a certain reaction is disturbed, the other reactions are also influenced since it is a connecting system coupled with co-enzymes/co-factors which also controls the metabolic process. In this study we numerically investigate the complex system by formulating a multi-enzymes and a multi-substrate kinetic model as a tool to study system regulatory opportunities. Based on the sensitivity analysis for the maximal reaction changes, the glucose transpose is predicted to yield the largest improvement in ethanol productivity while the reaction catalysed by acetaldehyde dehydrogenase is with the highest negative effect in reducing the amount of ethanol. The existence of NAD+ and NADH affect the performance of ethanol production that shows ups and downs behaviour when the maximal activity of some enzymes is disturbed. This is due to the inverse role of NADH and NAD+ in the certain reactions whether NAD+/NADH acts as a substrate or as a product.

Keywords

• fermentation
• multi substrate kinetic model
• runge-kutta numerical method
• sensitivity analysis