Protein engineering of Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase into parkeol synthase

Org Lett. 2012 Oct 19;14(20):5222-5. doi: 10.1021/ol302341h. Epub 2012 Oct 8.

Abstract

A Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase mutant, ERG7(T384Y/Q450H/V454I), produced parkeol but not lanosterol as the sole end product. Parkeol undergoes downstream metabolism to generate compounds 9 and 10. In vitro incubation of parkeol produced a product profile similar to that of the in vivo experiment. In summary, parkeol undergoes a metabolic pathway similar to that of cycloartenol in yeast but distinct from that of lanosterol in yeast, suggesting that two different metabolic pathways of postoxidosqualene cyclization may exist in S. cerevisiae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclization
  • Intramolecular Transferases / biosynthesis*
  • Intramolecular Transferases / chemistry
  • Intramolecular Transferases / genetics
  • Models, Molecular
  • Molecular Structure
  • Mutation
  • Protein Engineering
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Squalene / analogs & derivatives
  • Squalene / chemistry
  • Squalene / metabolism

Substances

  • oxidosqualene
  • Squalene
  • Intramolecular Transferases
  • lanosterol synthase