EasyClone 2.0: expanded toolkit of integrative vectors for stable gene expression in industrial Saccharomyces cerevisiae strains

J Ind Microbiol Biotechnol. 2015 Nov;42(11):1519-31. doi: 10.1007/s10295-015-1684-8. Epub 2015 Sep 16.

Abstract

Saccharomyces cerevisiae is one of the key cell factories for production of chemicals and active pharmaceuticals. For large-scale fermentations, particularly in biorefinery applications, it is desirable to use stress-tolerant industrial strains. However, such strains are less amenable for metabolic engineering than the standard laboratory strains. To enable easy delivery and overexpression of genes in a wide range of industrial S. cerevisiae strains, we constructed a set of integrative vectors with long homology arms and dominant selection markers. The vectors integrate into previously validated chromosomal locations via double cross-over and result in homogenous stable expression of the integrated genes, as shown for several unrelated industrial strains. Cre-mediated marker rescue is possible for removing markers positioned on different chromosomes. To demonstrate the applicability of the presented vector set for metabolic engineering of industrial yeast, we constructed xylose-utilizing strains overexpressing xylose isomerase, xylose transporter and five genes of the pentose phosphate pathway.

Keywords: Heterologous gene expression; Industrial yeast; Integrative vectors; Metabolic engineering; Xylose utilization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldose-Ketose Isomerases / genetics
  • Aldose-Ketose Isomerases / metabolism
  • Chromosomes, Fungal / genetics
  • Crossing Over, Genetic
  • Fermentation
  • Gene Expression Regulation, Fungal*
  • Genetic Engineering / methods*
  • Genetic Markers / genetics
  • Genetic Vectors / genetics*
  • Metabolic Engineering / methods
  • Pentose Phosphate Pathway / genetics
  • Saccharomyces cerevisiae / classification
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Xylose / metabolism

Substances

  • Genetic Markers
  • Xylose
  • Aldose-Ketose Isomerases
  • xylose isomerase