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Linking Genotype and Phenotype of Saccharomyces cerevisiae Strains Reveals Metabolic Engineering Targets and Leads to Triterpene Hyper-Producers

Karina M. Madsen ; D.B.R.K. Gupta Udatha (Institutionen för kemi- och bioteknik, Industriell Bioteknik ) ; Saori Semba ; José Manuel Otero Romero (Institutionen för kemi- och bioteknik) ; Peter Koetter ; Jens B. Nielsen (Institutionen för kemi- och bioteknik, Systembiologi) ; Yutaka Ebizuka ; Tetsuo Kushiro ; Gianni Panagiotou (Institutionen för kemi- och bioteknik, Industriell Bioteknik )
PLoS ONE (1932-6203). Vol. 6 (2011), 3, p. e14763.
[Artikel, refereegranskad vetenskaplig]

Background 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.



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Denna post skapades 2011-03-28. Senast ändrad 2014-10-27.
CPL Pubid: 138368

 

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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Industriell Bioteknik (2008-2014)
Institutionen för kemi- och bioteknik (2005-2014)
Institutionen för kemi- och bioteknik, Systembiologi (2008-2014)

Ämnesområden

Livsvetenskaper
Bioinformatik och systembiologi
Biokatalys och enzymteknik
Genteknik inkl. funktionsgenomik
Strukturbiokemi

Chalmers infrastruktur