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

<h4>Background</h4>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...

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Autores principales:	Karina M Madsen, Gupta D B R K Udatha, Saori Semba, Jose M Otero, Peter Koetter, Jens Nielsen, Yutaka Ebizuka, Tetsuo Kushiro, Gianni Panagiotou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d8c2384be40748d69cc732ffb8e789ba
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spelling	oai:doaj.org-article:d8c2384be40748d69cc732ffb8e789ba2021-11-18T06:57:08ZLinking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.1932-620310.1371/journal.pone.0014763https://doaj.org/article/d8c2384be40748d69cc732ffb8e789ba2011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21445244/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.Karina M MadsenGupta D B R K UdathaSaori SembaJose M OteroPeter KoetterJens NielsenYutaka EbizukaTetsuo KushiroGianni PanagiotouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e14763 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karina M Madsen Gupta D B R K Udatha Saori Semba Jose M Otero Peter Koetter Jens Nielsen Yutaka Ebizuka Tetsuo Kushiro Gianni Panagiotou Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.
format	article
author	Karina M Madsen Gupta D B R K Udatha Saori Semba Jose M Otero Peter Koetter Jens Nielsen Yutaka Ebizuka Tetsuo Kushiro Gianni Panagiotou
author_facet	Karina M Madsen Gupta D B R K Udatha Saori Semba Jose M Otero Peter Koetter Jens Nielsen Yutaka Ebizuka Tetsuo Kushiro Gianni Panagiotou
author_sort	Karina M Madsen
title	Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.
title_short	Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.
title_full	Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.
title_fullStr	Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.
title_full_unstemmed	Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.
title_sort	linking genotype and phenotype of saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/d8c2384be40748d69cc732ffb8e789ba
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Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.

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