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Article: Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers

TitleLinking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 3 How to Cite?
AbstractBackground: Metabolic engineering is an attractive approach in order to improve the microbial production of drugs. Triterpenes is a chemically diverse class of compounds and many among them are of interest from a human health perspective. A systematic experimental or computational survey of all feasible gene modifications to determine the genotype yielding the optimal triterpene production phenotype is a laborious and time-consuming process. Methodology/Principal Findings: Based on the recent genome-wide sequencing of Saccharomyces cerevisiae CEN.PK 113-7D and its phenotypic differences with the S288C strain, we implemented a strategy for the construction of a β-amyrin production platform. The genes Erg8, Erg9 and HFA1 contained non-silent SNPs that were computationally analyzed to evaluate the changes that cause in the respective protein structures. Subsequently, Erg8, Erg9 and HFA1 were correlated with the increased levels of ergosterol and fatty acids in CEN.PK 113-7D and single, double, and triple gene over-expression strains were constructed. Conclusions: The six out of seven gene over-expression constructs had a considerable impact on both ergosterol and β-amyrin production. In the case of β-amyrin formation the triple over-expression construct exhibited a nearly 500% increase over the control strain making our metabolic engineering strategy the most successful design of triterpene microbial producers. © 2011 Madsen et al.
Persistent Identifierhttp://hdl.handle.net/10722/181262
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMadsen, KMen_US
dc.contributor.authorUdatha, GDBRKen_US
dc.contributor.authorSemba, Sen_US
dc.contributor.authorOtero, JMen_US
dc.contributor.authorKoetter, Pen_US
dc.contributor.authorNielsen, Jen_US
dc.contributor.authorEbizuka, Yen_US
dc.contributor.authorKushiro, Ten_US
dc.contributor.authorPanagiotou, Gen_US
dc.date.accessioned2013-02-21T02:03:35Z-
dc.date.available2013-02-21T02:03:35Z-
dc.date.issued2011en_US
dc.identifier.citationPlos One, 2011, v. 6 n. 3en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10722/181262-
dc.description.abstractBackground: Metabolic engineering is an attractive approach in order to improve the microbial production of drugs. Triterpenes is a chemically diverse class of compounds and many among them are of interest from a human health perspective. A systematic experimental or computational survey of all feasible gene modifications to determine the genotype yielding the optimal triterpene production phenotype is a laborious and time-consuming process. Methodology/Principal Findings: Based on the recent genome-wide sequencing of Saccharomyces cerevisiae CEN.PK 113-7D and its phenotypic differences with the S288C strain, we implemented a strategy for the construction of a β-amyrin production platform. The genes Erg8, Erg9 and HFA1 contained non-silent SNPs that were computationally analyzed to evaluate the changes that cause in the respective protein structures. Subsequently, Erg8, Erg9 and HFA1 were correlated with the increased levels of ergosterol and fatty acids in CEN.PK 113-7D and single, double, and triple gene over-expression strains were constructed. Conclusions: The six out of seven gene over-expression constructs had a considerable impact on both ergosterol and β-amyrin production. In the case of β-amyrin formation the triple over-expression construct exhibited a nearly 500% increase over the control strain making our metabolic engineering strategy the most successful design of triterpene microbial producers. © 2011 Madsen 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.titleLinking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producersen_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.0014763en_US
dc.identifier.pmid21445244-
dc.identifier.scopuseid_2-s2.0-79952806663en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952806663&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume6en_US
dc.identifier.issue3en_US
dc.identifier.isiWOS:000288545100003-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridMadsen, KM=44561360700en_US
dc.identifier.scopusauthoridUdatha, GDBRK=37039920200en_US
dc.identifier.scopusauthoridSemba, S=44561436400en_US
dc.identifier.scopusauthoridOtero, JM=9842711900en_US
dc.identifier.scopusauthoridKoetter, P=8609105800en_US
dc.identifier.scopusauthoridNielsen, J=7404066338en_US
dc.identifier.scopusauthoridEbizuka, Y=7005685071en_US
dc.identifier.scopusauthoridKushiro, T=7005379970en_US
dc.identifier.scopusauthoridPanagiotou, G=8566179700en_US

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