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Article: Yeast biological networks unfold the interplay of antioxidants, genome and phenotype, and reveal a novel regulator of the oxidative stress response

TitleYeast biological networks unfold the interplay of antioxidants, genome and phenotype, and reveal a novel regulator of the oxidative stress response
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2010, v. 5 n. 10 How to Cite?
AbstractBackground: Identifying causative biological networks associated with relevant phenotypes is essential in the field of systems biology. We used ferulic acid (FA) as a model antioxidant to characterize the global expression programs triggered by this small molecule and decipher the transcriptional network controlling the phenotypic adaptation of the yeast Saccharomyces cerevisiae. Methodology/Principal Findings: By employing a strict cut off value during gene expression data analysis, 106 genes were found to be involved in the cell response to FA, independent of aerobic or anaerobic conditions. Network analysis of the system guided us to a key target node, the FMP43 protein, that when deleted resulted in marked acceleration of cellular growth (~15% in both minimal and rich media). To extend our findings to human cells and identify proteins that could serve as drug targets, we replaced the yeast FMP43 protein with its human ortholog BRP44 in the genetic background of the yeast strain δfmp43. The conservation of the two proteins was phenotypically evident, with BRP44 restoring the normal specific growth rate of the wild type. We also applied homology modeling to predict the 3D structure of the FMP43 and BRP44 proteins. The binding sites in the homology models of FMP43 and BRP44 were computationally predicted, and further docking studies were performed using FA as the ligand. The docking studies demonstrated the affinity of FA towards both FMP43 and BRP44. Conclusions: This study proposes a hypothesis on the mechanisms yeast employs to respond to antioxidant molecules, while demonstrating how phenome and metabolome yeast data can serve as biomarkers for nutraceutical discovery and development. Additionally, we provide evidence for a putative therapeutic target, revealed by replacing the FMP43 protein with its human ortholog BRP44, a brain protein, and functionally characterizing the relevant mutant strain. © 2010 Otero et al.
Persistent Identifierhttp://hdl.handle.net/10722/181258
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorOtero, JMen_US
dc.contributor.authorPapadakis, MAen_US
dc.contributor.authorGupta Udatha, DBRKen_US
dc.contributor.authorNielsen, Jen_US
dc.contributor.authorPanagiotou, Gen_US
dc.date.accessioned2013-02-21T02:03:33Z-
dc.date.available2013-02-21T02:03:33Z-
dc.date.issued2010en_US
dc.identifier.citationPlos One, 2010, v. 5 n. 10en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10722/181258-
dc.description.abstractBackground: Identifying causative biological networks associated with relevant phenotypes is essential in the field of systems biology. We used ferulic acid (FA) as a model antioxidant to characterize the global expression programs triggered by this small molecule and decipher the transcriptional network controlling the phenotypic adaptation of the yeast Saccharomyces cerevisiae. Methodology/Principal Findings: By employing a strict cut off value during gene expression data analysis, 106 genes were found to be involved in the cell response to FA, independent of aerobic or anaerobic conditions. Network analysis of the system guided us to a key target node, the FMP43 protein, that when deleted resulted in marked acceleration of cellular growth (~15% in both minimal and rich media). To extend our findings to human cells and identify proteins that could serve as drug targets, we replaced the yeast FMP43 protein with its human ortholog BRP44 in the genetic background of the yeast strain δfmp43. The conservation of the two proteins was phenotypically evident, with BRP44 restoring the normal specific growth rate of the wild type. We also applied homology modeling to predict the 3D structure of the FMP43 and BRP44 proteins. The binding sites in the homology models of FMP43 and BRP44 were computationally predicted, and further docking studies were performed using FA as the ligand. The docking studies demonstrated the affinity of FA towards both FMP43 and BRP44. Conclusions: This study proposes a hypothesis on the mechanisms yeast employs to respond to antioxidant molecules, while demonstrating how phenome and metabolome yeast data can serve as biomarkers for nutraceutical discovery and development. Additionally, we provide evidence for a putative therapeutic target, revealed by replacing the FMP43 protein with its human ortholog BRP44, a brain protein, and functionally characterizing the relevant mutant strain. © 2010 Otero et al.en_US
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_US
dc.relation.ispartofPLoS ONEen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAntioxidants - Metabolismen_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshFungal Proteins - Metabolismen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshGene Expression Regulation, Fungalen_US
dc.subject.meshGenome, Fungalen_US
dc.subject.meshHumansen_US
dc.subject.meshMetabolomeen_US
dc.subject.meshOligonucleotide Array Sequence Analysisen_US
dc.subject.meshOxidative Stressen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshSaccharomyces Cerevisiae - Genetics - Metabolismen_US
dc.subject.meshTranscription, Geneticen_US
dc.titleYeast biological networks unfold the interplay of antioxidants, genome and phenotype, and reveal a novel regulator of the oxidative stress responseen_US
dc.typeArticleen_US
dc.identifier.emailPanagiotou, G: gipa@hku.hken_US
dc.identifier.authorityPanagiotou, G=rp01725en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0013606en_US
dc.identifier.pmid21049050-
dc.identifier.scopuseid_2-s2.0-78149439957en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78149439957&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume5en_US
dc.identifier.issue10en_US
dc.identifier.isiWOS:000283422100014-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridOtero, JM=9842711900en_US
dc.identifier.scopusauthoridPapadakis, MA=24475503600en_US
dc.identifier.scopusauthoridGupta Udatha, DBRK=36620921000en_US
dc.identifier.scopusauthoridNielsen, J=7404066338en_US
dc.identifier.scopusauthoridPanagiotou, G=8566179700en_US

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