TY - JOUR
T1 - A systems biology approach to study glucose repression in the yeast Saccharomyces cerevisiae
AU - Westergaard, Steen Lund
AU - Soberano de Oliveira, Ana Paula
AU - Bro, Christoffer
AU - Olsson, Lisbeth
AU - Nielsen, Jens
PY - 2007
Y1 - 2007
N2 - Glucose repression in the yeast Saccharomyces cerevisiae has evolved as a complex regulatory system involving several different pathways. There are two main pathways involved in signal transduction. One has a role in glucose sensing and regulation of glucose transport, while another takes part in repression of a wide range of genes involved to utilization of alternative carbon sources. In this work, we applied a systems biology approach to study the interaction between these two pathways. Through genome-wide transcription analysis of strains with disruption of HXK2, GRR1, MIG1, the combination of MIG1 and MIG2, and the parentel strain, we identified 393 genes to have significantly changed expression levels. To identify co-regulation patterns in the different strains we applied principal component analysis. Disruption of either GRR1 or HXK2 were both found to have profound effects on transcription of genes telated to TCA cycle and respiration, as well as ATP synthesis coupled proton transport, all displaying an increased expression. The hxk2Δ strain showed reduced overflow metabolism towards ethanol relative to the parental strain. We also used a genome-scale metabolic model to identify reporter metabolites, and found that there is a high degree of consistency between the identified reporter metabolites and the physiological effects observed in the different mutants . Our systems biology approach points to close interaction between the two pathways, and our metabolism driven analysis of transcription data may find a wider application for analysis of cross-talk between different pathways involved in regulation of metabolism. © 2006 Wiley Periodicals, Inc.
AB - Glucose repression in the yeast Saccharomyces cerevisiae has evolved as a complex regulatory system involving several different pathways. There are two main pathways involved in signal transduction. One has a role in glucose sensing and regulation of glucose transport, while another takes part in repression of a wide range of genes involved to utilization of alternative carbon sources. In this work, we applied a systems biology approach to study the interaction between these two pathways. Through genome-wide transcription analysis of strains with disruption of HXK2, GRR1, MIG1, the combination of MIG1 and MIG2, and the parentel strain, we identified 393 genes to have significantly changed expression levels. To identify co-regulation patterns in the different strains we applied principal component analysis. Disruption of either GRR1 or HXK2 were both found to have profound effects on transcription of genes telated to TCA cycle and respiration, as well as ATP synthesis coupled proton transport, all displaying an increased expression. The hxk2Δ strain showed reduced overflow metabolism towards ethanol relative to the parental strain. We also used a genome-scale metabolic model to identify reporter metabolites, and found that there is a high degree of consistency between the identified reporter metabolites and the physiological effects observed in the different mutants . Our systems biology approach points to close interaction between the two pathways, and our metabolism driven analysis of transcription data may find a wider application for analysis of cross-talk between different pathways involved in regulation of metabolism. © 2006 Wiley Periodicals, Inc.
U2 - 10.1002/bit.21135
DO - 10.1002/bit.21135
M3 - Journal article
C2 - 16878332
SN - 0006-3592
VL - 96
SP - 134
EP - 145
JO - Biotechnology and Bioengineering (Print)
JF - Biotechnology and Bioengineering (Print)
IS - 1
ER -