AN INDIRECT OPTIMIZATION METHOD FOR BIOCHEMICAL SYSTEMS - DESCRIPTIONOF METHOD AND APPLICATION TO THE MAXIMIZATION OF THE RATE OF ETHANOL,GLYCEROL, AND CARBOHYDRATE PRODUCTION IN SACCHAROMYCES-CEREVISIAE

Three metabolic models for the production of ethanol, glycerol, and ca rbohydrates in yeast are optimized with respect to different productio n rates. While originally nonlinear, all three optimization problems a re reduced in such a way that methods of linear programming can be use d. The optimizations lead to profiles of enzyme activities that are co mpatible with the physiology of the cells, which guarantees their viab ility and fitness, and yield higher rates of the desired final end pro ducts than the original systems. In order to increase ethanol rate pro duction at least three times, six enzymes must be modulated. By contra st, when the production of glycerol or carbohydrates is optimized, mod ulation of just one enzyme (in the case of glycerol) or two enzymes (i n the case of carbohydrates) is necessary to yield significant increas es in product flux rate. Comparisons of our results-with those obtaine d from other methods show great similarities and demonstrate that both are valid methods. The choice of one or the other method depends on t he question of interest. (C) 1997 John Wiley & Sons, Inc.