Metabolite profiling studies in Saccharomyces cerevisiae: an assisting tool to prioritize host targets for antiviral drug screening
Identifieur interne : 000D72 ( Main/Exploration ); précédent : 000D71; suivant : 000D73Metabolite profiling studies in Saccharomyces cerevisiae: an assisting tool to prioritize host targets for antiviral drug screening
Auteurs : Konstantin Schneider [Allemagne] ; Jens Olaf Krömer [Allemagne, Australie] ; Christoph Wittmann [Allemagne] ; Isabel Alves-Rodrigues [Espagne] ; Andreas Meyerhans [Allemagne] ; Juana Diez [Allemagne, Espagne] ; Elmar Heinzle [Allemagne]Source :
- Microbial Cell Factories [ 1475-2859 ] ; 2009.
Abstract
The cellular proteins Pat1p, Lsm1p, and Dhh1p are required for the replication of some positive-strand viruses and therefore are potential targets for new antiviral drugs. To prioritize host targets for antiviral drug screening a comparative metabolome analysis in
GC/MS analysis permitted the quantification of 47 polar metabolites and the identification of 41 of them. Metabolites with significant variation between the strains were identified using partial least squares to latent structures discriminate analysis (PLS-DA). The analysis revealed least differences of
From these results we hypothesize that the human analog of yeast Pat1p is most likely the best drug target candidate.
Url:
DOI: 10.1186/1475-2859-8-12
PubMed: 19183481
PubMed Central: 2658664
Affiliations:
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last="Schneider">Konstantin Schneider</name><affiliation wicri:level="3"><nlm:aff id="I1">Biochemical Engineering Institute, Saarland University, 66123 Saarbrucken, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Biochemical Engineering Institute, Saarland University, 66123 Saarbrucken</wicri:regionArea><placeName><region type="land" nuts="2">Sarre (Land)</region><settlement type="city">Sarrebruck</settlement></placeName></affiliation></author><author><name sortKey="Kromer, Jens Olaf" sort="Kromer, Jens Olaf" uniqKey="Kromer J" first="Jens Olaf" last="Krömer">Jens Olaf Krömer</name><affiliation wicri:level="3"><nlm:aff id="I1">Biochemical Engineering Institute, Saarland University, 66123 Saarbrucken, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Biochemical Engineering Institute, Saarland University, 66123 Saarbrucken</wicri:regionArea><placeName><region type="land" nuts="2">Sarre (Land)</region><settlement 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Barcelona</wicri:regionArea><placeName><region nuts="2" type="communauté">Catalogne</region></placeName></affiliation></author><author><name sortKey="Meyerhans, Andreas" sort="Meyerhans, Andreas" uniqKey="Meyerhans A" first="Andreas" last="Meyerhans">Andreas Meyerhans</name><affiliation wicri:level="1"><nlm:aff id="I2">Institute of Virology, Saarland University, 66421 Homburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Saarland University, 66421 Homburg</wicri:regionArea><wicri:noRegion>66421 Homburg</wicri:noRegion><wicri:noRegion>66421 Homburg</wicri:noRegion><wicri:noRegion>66421 Homburg</wicri:noRegion></affiliation></author><author><name sortKey="Diez, Juana" sort="Diez, Juana" uniqKey="Diez J" first="Juana" last="Diez">Juana Diez</name><affiliation wicri:level="1"><nlm:aff id="I2">Institute of Virology, Saarland University, 66421 Homburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Saarland University, 66421 Homburg</wicri:regionArea><wicri:noRegion>66421 Homburg</wicri:noRegion><wicri:noRegion>66421 Homburg</wicri:noRegion><wicri:noRegion>66421 Homburg</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="I3">Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona</wicri:regionArea><placeName><region nuts="2" type="communauté">Catalogne</region></placeName></affiliation></author><author><name sortKey="Heinzle, Elmar" sort="Heinzle, Elmar" uniqKey="Heinzle E" first="Elmar" last="Heinzle">Elmar Heinzle</name><affiliation wicri:level="3"><nlm:aff id="I1">Biochemical Engineering Institute, Saarland University, 66123 Saarbrucken, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Biochemical Engineering Institute, 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To prioritize host targets for antiviral drug screening a comparative metabolome analysis in <italic>Saccharomyces cerevisiae </italic>reference strain BY4742 <italic>Matα his3Δ1 leu2Δ0 lys2Δ0 ura3Δ0 </italic>and deletion strains <italic>pat1Δ</italic>, <italic>lsm1Δ </italic>and <italic>dhh1Δ </italic>was performed.</p></sec><sec><title>Results</title><p>GC/MS analysis permitted the quantification of 47 polar metabolites and the identification of 41 of them. Metabolites with significant variation between the strains were identified using partial least squares to latent structures discriminate analysis (PLS-DA). The analysis revealed least differences of <italic>pat1Δ </italic>to the reference strain as characterized by Euclidian distance of normalized peak areas. The growth rate and specific production rates of ethanol and glycerol were also most similar with this strain.</p></sec><sec><title>Conclusion</title><p>From these results we hypothesize that the human analog of yeast Pat1p is most likely the best drug target candidate.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Espagne</li></country><region><li>Catalogne</li><li>Sarre (Land)</li></region><settlement><li>Sarrebruck</li></settlement></list><tree><country name="Allemagne"><region name="Sarre (Land)"><name sortKey="Schneider, Konstantin" sort="Schneider, Konstantin" uniqKey="Schneider K" first="Konstantin" last="Schneider">Konstantin Schneider</name></region><name sortKey="Diez, Juana" sort="Diez, Juana" uniqKey="Diez J" first="Juana" last="Diez">Juana Diez</name><name sortKey="Heinzle, Elmar" sort="Heinzle, Elmar" uniqKey="Heinzle E" first="Elmar" last="Heinzle">Elmar Heinzle</name><name sortKey="Kromer, Jens Olaf" sort="Kromer, Jens Olaf" uniqKey="Kromer J" first="Jens Olaf" last="Krömer">Jens Olaf Krömer</name><name sortKey="Meyerhans, Andreas" sort="Meyerhans, Andreas" uniqKey="Meyerhans A" first="Andreas" last="Meyerhans">Andreas Meyerhans</name><name sortKey="Wittmann, Christoph" sort="Wittmann, Christoph" uniqKey="Wittmann C" first="Christoph" last="Wittmann">Christoph Wittmann</name><name sortKey="Wittmann, Christoph" sort="Wittmann, Christoph" uniqKey="Wittmann C" first="Christoph" last="Wittmann">Christoph Wittmann</name></country><country name="Australie"><noRegion><name sortKey="Kromer, Jens Olaf" sort="Kromer, Jens Olaf" uniqKey="Kromer J" first="Jens Olaf" last="Krömer">Jens Olaf Krömer</name></noRegion></country><country name="Espagne"><region name="Catalogne"><name sortKey="Alves Rodrigues, Isabel" sort="Alves Rodrigues, Isabel" uniqKey="Alves Rodrigues I" first="Isabel" last="Alves-Rodrigues">Isabel Alves-Rodrigues</name></region><name sortKey="Diez, Juana" sort="Diez, Juana" uniqKey="Diez J" first="Juana" last="Diez">Juana Diez</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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