AN INVESTIGATION OF THE AEROBIC, GLUCOSE-LIMITED GROWTH AND DYNAMICS OF SACCHAROMYCES CEREVISIAE
Abstract
The full power of computer-coupled fermentor systems can be realized only when accurate, mechanistic (structured) process models are developed. The objective of this research was to develop a structured mathematical model for the aerobic, glucose-limited growth of Saccharomyces cerevisiae. Emphasis was placed on minimizing the dependence of the model on intracellular variables which are not readily measured. Several important mechanisms in the growth of S. cerevisiae were identified: (1) the fermentative and oxidative pathways involved in the catabolism of glucose and ethanol, (2) the Crabtree effect, a genetic-level control mechanism, (3) the modulation of the catabolic pathways, (4) the asymmetric dynamic response, and (5) the dynamic nature of growth at the level of individual cells. Continuous culture experiments were conducted to further study these phenomena. The results showed that the Crabtree effect is closely related to the specific glucose consumption rate. Continuous culture dynamic responses often resulted in stable, sustained oscillations due to population synchrony. These are caused by changes in oxidative metabolism which disrupt the structure of the cell cycle. The asymmetric dynamic response describes a variable growth limitation widely observed in microbial systems. A general model was formulated; it includes dynamic rate expressions for cell mass synthesis and the synthesis of enzymes subject to genetic-level control. The active rate expressions are determined by the relationship of a specific synthesis rate to its target value. The model is simple, but has considerable predictive power. Two specific models for the growth of S. cerevisiae were formulated: a structured, non-segregated model and a population balance model. The former closely fits steady state data and describes the asymmetric dynamic response in S. cerevisiae. It has some predictive power, but its accounting for the documented growth mechanisms is incomplete. The population balance model is an extension of the non-segregated model; it accounts, in addition, for the structure of the cell cycle. Steady state simulation results showed it to be a good starting point for describing the population-based dynamic responses.
Degree
Ph.D.
Subject Area
Chemical engineering
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