Reconstruction and evaluation of the synthetic bacterial MEP pathway in Saccharomyces cerevisiae

PLoS One. 2012;7(12):e52498. doi: 10.1371/journal.pone.0052498. Epub 2012 Dec 28.

Abstract

Isoprenoids, which are a large group of natural and chemical compounds with a variety of applications as e.g. fragrances, pharmaceuticals and potential biofuels, are produced via two different metabolic pathways, the mevalonate (MVA) pathway and the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we attempted to replace the endogenous MVA pathway in Saccharomyces cerevisiae by a synthetic bacterial MEP pathway integrated into the genome to benefit from its superior properties in terms of energy consumption and productivity at defined growth conditions. It was shown that the growth of a MVA pathway deficient S. cerevisiae strain could not be restored by the heterologous MEP pathway even when accompanied by the co-expression of genes erpA, hISCA1 and CpIscA involved in the Fe-S trafficking routes leading to maturation of IspG and IspH and E. coli genes fldA and fpr encoding flavodoxin and flavodoxin reductase believed to be responsible for electron transfer to IspG and IspH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Electron Transport
  • Erythritol / analogs & derivatives*
  • Erythritol / metabolism
  • Escherichia coli / metabolism*
  • Genes, Fungal / genetics
  • Genetic Engineering*
  • Iron-Sulfur Proteins / metabolism
  • Metabolic Networks and Pathways*
  • Mevalonic Acid / metabolism
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Sugar Phosphates / metabolism*

Substances

  • 2-C-methylerythritol 4-phosphate
  • Iron-Sulfur Proteins
  • Sugar Phosphates
  • Erythritol
  • Mevalonic Acid

Grants and funding

The Knut and Alice Wallenberg Foundation, the Chalmers Foundation and Firmenich AG have financially supported this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.