Abstract
When Saccharomyces cerevisiae undergoes heat stress it stimulates several changes that are necessary for its survival, notably in carbon metabolism. Notable changes include increase in trehalose production and glycolytic flux. The increase in glycolytic flux has been postulated to be due to the regulatory effects in upper glycolysis, but this has not been confirmed. Additionally, trehalose is a useful industrial compound for its protective properties. A model of trehalose metabolism in S. cerevisiae was constructed using Convenient Modeller, a software that uses a combination of convenience kinetics and a genetic algorithm. The model was parameterized with quantitative omics under standard conditions and validated using data collected under heat stress conditions. The completed model was used to show that feedforward activation of pyruvate kinase by fructose 1,6-bisphosphate during heat stress contributes to the increase in metabolic flux. We were also able to demonstrate in silico that overexpression of enzymes involved in production and degradation of trehalose can lead to higher trehalose yield in the cell. By integrating quantitative proteomics with metabolic modelling, we were able to confirm that the flux increase in trehalose metabolic pathways during heat stress is due to regulatory effects and not purely changes in enzyme expression. The overexpression of enzymes involved in trehalose metabolism is a potential approach to be exploited for trehalose production without need for increasing temperature.
Highlights
Trehalose has often been associated with the eukaryotic model organism baker’s yeast during heat stress, as the microbe is observed to accumulate high concentrations of this protective molecule for survival [1,2,3]
Convenient Modeller is a tool for building kinetic models for cell metabolism, requiring input from the users on the substrates and products involved in the metabolic reactions and the enzymes that catalyse the reactions, which are translated into rate equations automatically
A kinetic model focusing on trehalose metabolism parameterized with quantitative metabolite concentrations, flux, and protein abundance data collected before heat stress was applied to the cells, is presented here
Summary
Trehalose has often been associated with the eukaryotic model organism baker’s yeast during heat stress, as the microbe is observed to accumulate high concentrations of this protective molecule for survival [1,2,3]. The protective nature of trehalose is due to it being a stable and generally unreactive sugar, acting as a robust energy storage vehicle [4]. Owing to the aforementioned protective properties, trehalose has high commercial value as it is used in various industries from pharmaceuticals to food and cosmetics [4,5,6]. In the pharmaceutical industry trehalose has been used for the storage of vaccine at room temperature as it has been found to stabilise vaccines. Trehalose serves as liposome stabilizer and as stable sweetener for food. Its production in the industry relies on the use of enzymes from extremophiles expressed in other microbes [6]
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