A Simulation Study on Model-Based Optimization of Intracellular Trehalose Accumulation in Saccharomyces cerevisiae Fed-Batch Cultures

Abstract

Trehalose is a reserve carbohydrate, which occurs naturally in yeast and acts as a stress protectant for cells. Due to its features, trehalose is used in many industries (food, biopharmaceuticals, cosmetics). Its production/accumulation may be triggered and enhanced by the culture operating conditions, among which the feed flow rate and the start of the starvation period play the most important role. This paper presents a simulation study based on a novel model validated with experimental data, highlighting the interplay between trehalose maximization and biomass maximization. Several single-objective and multi-objective constrained optimization problems are solved using the control vector parameterization approach. It is shown that maximizing either the trehalose concentration or the biomass amount leads to solutions which are not appealing in practice. The best solution is obtained by maximizing trehalose concentration with a lower bound on the biomass amount. A comparison of the optimal solution to experimental data reveals that, although approximately the same amount of biomass can be obtained with different feeding profiles and starvation times, the maximization of trehalose concentration requires feeding most of the culture medium in the first part of the experiment while starting the nitrogen starvation at an early stage.