Non-linear optimization of biotechnological processes by stochastic algorithms: application to the maximization of the production rate of ethanol, glycerol and carbohydrates by Saccharomyces cerevisiae.

A non-linear optimization, based on an stochastic multi-start search algorithm, has been applied to the maximization of the production rates of ethanol, glycerol and carbohydrates by Saccharomyces cerevisiae. This optimization is applied to two alternative (non-linear) model representations of the same system, namely the Michaelis-Menten and the generalized mass action forms. We find a complete agreement between the results obtained using both representations. This is, maximization of the ethanol production rate requires modulation of up to six enzymes, while modification of only one enzyme is sufficient to obtain a significant improvement in the production rate of glycerol and carbohydrates. When the results are compared with those previously obtained using an indirect linear optimization method (Torres, N.V., Voit, E.O., González-Alcón, C., Rodríguez, F. 1997. An integrated optimization method for biochemical systems. Description of method and application to ethanol, glycerol and carbohydrate production in S. cerevisiae. Biotechnol. Bioeng. 55(5), 758-772.), we find close agreement between both optimization techniques. Qualitatively, both optimization approaches render the same profile of enzymes to be modulated, while quantitatively, discrepancies arise when the objective function is the maximization of the ethanol production rate. Reasons for such discrepancies and an evaluation of the advantages of each method (linear vs non-linear) are given.