Glucose control in Saccharomyces cerevisiae: the role of MIG1 in metabolic functions

Abstract

OverviewIndustrial cultivation media, such as molasses, wort, agricultural waste and lignocellulose hydrolysates, contain a mixture of metabolizable carbohydrates. These carbohydrates are taken up by cells in a certain order with intermittent lag phases due to a set of mechanisms controlled by glucose, referred to hereafter as glucose control. Thus, the presence or uptake of glucose has a negative impact upon the metabolism of other sugars. Glucose repression reduces the transcription rate of repressible genes, and is the most thoroughly investigated mechanism of glucose control (Fig. 1).In this review the different mechanisms of glucose control in Saccharomyces cereuisiae are first discussed, focusing on the mechanism of glucose repression. Next, the function of the regulatory protein Migl in the signalling cascade of glucose repression is explained. The impact of Migl-mediated glucose repression on metabolic functions is then discussed. It will be made clear that glucose repression is not confined to the above-mentioned example of mixed sugar metabolism. The last part of the review summarizes the effects glucose repression has on single metabolic functions. These components are then linked to a holistic view with the aim of understanding the effects of Migl on overall metabolism. Against this background possible physiological impacts of deletion/disruption of the MZGl gene are discussed.Glucose control in 5. cerevisiae

Progress in Metabolic Engineering of Saccharomyces cerevisiae

“…For more details concerning these previous examples of engineering baker's yeast, the reader is referred to the reviews mentioned at the beginning of this section. There have been also attempts to alleviate glucose repression of maltose-utilizing enzymes by deleting proteins which act as transcriptional regulators, such as Mig1p (168,169).…”

Nsf1/Ypl230w participates in transcriptional activation during non-fermentative growth and in response to salt stress in Saccharomyces cerevisiae

“…In contrast, when glucose is limiting or only non-fermentable carbon sources are present, Snf1 is phosphorylated and found in its activated conformation (Jiang & Carlson, 1996). Active Snf1 phosphorylates Mig1, which exits the nucleus, thereby enabling the derepression of glucose-repressible genes such as members of the GAL and MAL gene families and the transcriptional activator CAT8 (DeVit & Johnston, 1999;Hedges et al, 1995;Klein et al, 1998;Mercado et al, 1991;Scholer & Schuller, 1993;Schuller, 2003;Treitel et al, 1998). In addition, active Snf1 enables the binding of the transcriptional activator Adr1 to DNA (Young et al, 2002).…”

Investigation by 13C-NMR and tricarboxylic acid (TCA) deletion mutant analysis of pathways for succinate formation in Saccharomyces cerevisiae during anaerobic fermentation

“…In anaerobic glucose fermentation, the enzymes of the TCA pathway are repressed by both glucose and hypoxia. Several genes may be indirectly regulated by the DNA-binding repressor Mig1p, a key protein in the signalling cascade of glucose repression (Klein et al, 1998). CIT1 and CIT3, which encode the mitochondrial citrate synthase (responsible for catalysing the first step in the TCA cycle), and KGD1, KGD2 and LPD1, which encode the oxoglutarate dehydrogenase (OGDH) complex, are activated by Hap4, a transcription factor under the control of Mig1p (de Winde & Grivell, 1993;Rosenkrantz et al, 1994).…”