TY - JOUR

T1 - Genome-wide transcriptional response of a Saccharomyces cerevisiae strain with an altered redox metabolism

AU - Bro, Christoffer

AU - Regenberg, Birgitte

AU - Nielsen, Jens

PY - 2004

Y1 - 2004

N2 - The genome-wide transcriptional response of a Saccharomyces cerevisiae strain deleted in GDH1 that encodes a NADP+-dependent glutamate dehydrogenase was compared to a wild-type strain under anaerobic steady-state conditions. The GDH1-deleted strain has a significantly reduced NADPH requirement, and therefore, an altered redox metabolism. Identification of genes with significantly changed expression using a t-test and a Bonferroni correction yielded only 16 transcripts when accepting two false-positives, and 7 of these were Open Reading Frames (ORFs) with unknown function. Among the 16 transcripts the only one with a direct link to redox metabolism was GND1, encoding phosphogluconate dehydrogenase. To extract additional information we analyzed the transcription data for a gene subset consisting of all known genes encoding metabolic enzymes that use NAD+ or NADP+. The subset was analyzed for genes with significantly changed expression again with a t-test and correction for multiple testing. This approach was found to enrich the analysis since GND1, ZWF1 and ALD6, encoding the most important enzymes for regeneration of NADPH under anaerobic conditions, were down-regulated together with eight other genes encoding NADP(H)-dependent enzymes. This indicates a possible common redoxdependent regulation of these genes. Furthermore, we showed that it might be necessary to analyze the expression of a subset of genes to extract all available information from global transcription analysis.

AB - The genome-wide transcriptional response of a Saccharomyces cerevisiae strain deleted in GDH1 that encodes a NADP+-dependent glutamate dehydrogenase was compared to a wild-type strain under anaerobic steady-state conditions. The GDH1-deleted strain has a significantly reduced NADPH requirement, and therefore, an altered redox metabolism. Identification of genes with significantly changed expression using a t-test and a Bonferroni correction yielded only 16 transcripts when accepting two false-positives, and 7 of these were Open Reading Frames (ORFs) with unknown function. Among the 16 transcripts the only one with a direct link to redox metabolism was GND1, encoding phosphogluconate dehydrogenase. To extract additional information we analyzed the transcription data for a gene subset consisting of all known genes encoding metabolic enzymes that use NAD+ or NADP+. The subset was analyzed for genes with significantly changed expression again with a t-test and correction for multiple testing. This approach was found to enrich the analysis since GND1, ZWF1 and ALD6, encoding the most important enzymes for regeneration of NADPH under anaerobic conditions, were down-regulated together with eight other genes encoding NADP(H)-dependent enzymes. This indicates a possible common redoxdependent regulation of these genes. Furthermore, we showed that it might be necessary to analyze the expression of a subset of genes to extract all available information from global transcription analysis.

KW - Bioinformatics

KW - DNA arrays

KW - Ethanol production

KW - Metabolic engineering

KW - Transcription analysis

U2 - 10.1002/bit.10899

DO - 10.1002/bit.10899

M3 - Journal article

C2 - 14748081

AN - SCOPUS:0842278678

VL - 85

SP - 269

EP - 276

JO - Biotechnology and Bioengineering

JF - Biotechnology and Bioengineering

SN - 0006-3592

IS - 3

ER -