Mixed and diverse metabolic and gene-expression regulation of the glycolytic and fermentative pathway in response to a HAP4 overexpression in Saccharomyces cerevisiae

S. Rossell, P.A. Lindenbergh, C.C. van der Weijden, A.L. Kruckeberg, K. van Eunen, H.V. Westerhoff, B.M. Bakker

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

In Saccharomyces cerevisiae the HXK2 gene, which encodes the glycolytic enzyme hexokinase II, is involved in the regulatory mechanism known as ‘glucose repression’. Its deletion leads to fully respiratory growth at high glucose concentrations where the wild type ferments profusely. Here we describe that deletion of the HXK2 gene resulted in a 75% reduction in fermentative capacity. Using regulation analysis we found that the fluxes through most glycolytic and fermentative enzymes were regulated cooperatively by changes in their capacities (Vmax) and by changes in the way they interacted with the rest of the metabolism. Glucose transport and phosphofructokinase were regulated purely at the metabolic level. The reduction of fermentative capacity in the mutant was accompanied by a remarkable resilience of the remaining capacity to nutrient starvation. After starvation, the fermentative capacity of the hxk2Δ mutant was similar to that of the wild type. Based on our results and previous reports, we suggest an inverse correlation between glucose repression and the resilience of fermentative capacity towards nutrient starvation. Only a limited number of glycolytic enzyme activities changed upon starvation of the hxk2Δ mutant and we discuss to what extent this could explain the stability of the fermentative capacity.
Original languageEnglish
Pages (from-to)155–164
Number of pages10
JournalFEMS Yeast Research
Volume8
Issue number1
Early online date1 Feb 2008
DOIs
Publication statusPublished - Feb 2008

Bibliographical note

Working title: Mixed and diverse metabolic and gene-expression regulation of the glycolytic and fermentative pathway in response to a HAP4 overexpression in Saccharomyces cerevisiae

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