Quantitative analysis of the regulation scheme of invertase expression in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, the expression of invertase, which is the hydr olyzing enzyme of sucrose, is controlled by the presence of monosaccharides , such as glucose and fructose, and referred to as carbon catabolite repres sion. To date, efforts have been made to identify the mechanism by which ce lls sense extracellular monosaccharide concentrations and trigger the genes involved in the repression pathway. The aim of the present work was to qua ntitatively investigate the cellular regulation of invertase expression in the wild-type strain S. cerevisiae CEN.PK113-7D during batch growth contain ing mixed sugar substrates under different initial conditions. Because of the high frequency and accurate online analysis of multiple comp onents, a tight control of invertase expression could be observed, and thre shold concentrations of the monosaccharicles for derepression could be dete rmined to 0.5 gl(-1) for glucose and 2 gl(-1) for fructose. Also, the exist ence of a hitherto undescribed regulatory state, in which cells regulate in vertase expression very precisely and operate over long periods at monosacc haride concentrations lower than the above thresholds, could be demonstrate d. All experimental observations could be summarized in a formulation of th e cellular regulation scheme of invertase expression. A simple kinetic mode l could show that the regulation scheme explains the observed behavior very well. Additionally, the model was able to explain consequences of the regu lation on the global metabolism. (C) 2001 John Wiley & Sons, Inc.