Nitrogen-limited continuous cultivations as a tool to quantify glucose control in Saccharomyces cerevisiae

Abstract

In Saccharomyces cerevisiae, glucose can control (reduce) the activity level of a metabolically crucial protein by either regulating the expression of the encoding gene or affecting the protein itself. The five possible mechanisms operative are: transcriptional glucose repression, an increased decay of mRNA, a decreased efficiency of translation, carbon catabolite inactivation, and competitive inhibition by glucose. In this paper, a simple, empirical model is presented that quantifies the impact of glucose on the metabolism of other sugars (e.g., maltose) by a negative exponential term with only one parameter, the glucose control parameter. Glucose control on maltose metabolism was investigated in nitrogen-limited continuous cultures of S. cerevisiae with glucose-maltose mixtures as the carbon and energy source, assessing the model and estimating the glucose control parameter. Using the estimated values of the glucose control parameters for two different S. cerevisiae strains (an industrial strain and its Δ mig1 transformant), batch cultivations on glucose-maltose mixtures were simulated and compared with experimental data. Finally, the distribution of flux control between the maltose uptake and subsequent hydrolysis to glucose was calculated. For both strains, it was confirmed that flux control was likely to be mainly exerted by maltose uptake (maltose permease), and this effect increased with rising concentrations of glucose in the medium. As a crucial difference between the two strains, maltose consumption in the MIG1-disrupted strain was more stringently controlled by maltose permease than in the wildtype strain.