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

Madsen, Karina M.Danmarks Tekniske Universitet,Technical University of Denmark (författare)

BackgroundMetabolic 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 FindingsBased 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.ConclusionsThe 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.

Udatha, Gupta,1984Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)udatha (författare)
Semba, SaoriUniversity of Tokyo, Japan (författare)
Otero, José Manuel,1979Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)mjose (författare)
Koetter, PeterJohann Wolfgang Goethe Universität Frankfurt am Main,Goethe University Frankfurt (författare)
Nielsen, Jens B,1962Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj (författare)
Ebizuka, YutakaUniversity of Tokyo, Japan (författare)
Kushiro, TetsuoUniversity of Tokyo, Japan (författare)
Panagiotou, Gianni,1974Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)gianni (författare)
Danmarks Tekniske UniversitetChalmers tekniska högskola (creator_code:org_t)

Ingår i:PLoS ONE: Public Library of Science (PLoS)6:3, s. e14763-1932-62031932-6203

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