title: Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers.
abstract: 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.
  
  
  RESULTS
  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.
authors: Center for Microbial Biotechnology, Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors: Karina M
authors: KM
authors: Madsen
authors: Gupta D B R K
authors: GD
authors: Udatha
authors: Saori
authors: S
authors: Semba
authors: Jose M
authors: JM
authors: Otero
authors: Peter
authors: P
authors: Koetter
authors: Jens
authors: J
authors: Nielsen
authors: Yutaka
authors: Y
authors: Ebizuka
authors: Tetsuo
authors: T
authors: Kushiro
authors: Gianni
authors: G
authors: Panagiotou
mesh_terms: D001665:Binding Sites; D005838:Genotype; D008958:Models, Molecular; D010641:Phenotype; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D014315:Triterpenes / Q000378:metabolism*
chemical_list: D014315:Triterpenes; D017856:Phosphotransferases (Phosphate Group Acceptor); C022371:phosphomevalonate kinase