Preparation of 20-HETE using multifunctional enzyme type 2-negative Starmerella bombicola

J Lipid Res. 2013 Nov;54(11):3215-9. doi: 10.1194/jlr.D042226. Epub 2013 Aug 21.

Abstract

The metabolism of arachidonic acid (ARA) by cytochrome P450 ω/ω-1-hydroxylases leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), which is an important lipid-signaling molecule involved in regulation of vascular tone, angiogenesis, and inflammation. Development of a simple method to prepare 20-HETE would greatly facilitate the investigation of its biological activities. The nonpathogenic yeast Starmerella bombicola has been shown to convert exogenously added arachidonic acid to 20-HETE via the biosynthetic pathway of sophorolipids; however, the yield was low. Here we demonstrate that genetic knockout of multifunctional enzyme type 2 (MFE-2), which is involved in the β-oxidation of fatty acids, significantly increases the yield of ARA conversion to 20-HETE and allows practical preparation of 20-HETE.

Keywords: 20-hydroxyeicosatetraenoic acid; arachidonic acid; sophorolipids.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Ascomycota / enzymology*
  • Cytochrome P-450 Enzyme System / metabolism
  • Gene Knockout Techniques*
  • Hydroxyeicosatetraenoic Acids / biosynthesis*
  • Hydroxyeicosatetraenoic Acids / metabolism
  • Hydroxyeicosatetraenoic Acids / pharmacology
  • Hydroxylation
  • Hydroxysteroid Dehydrogenases / deficiency*
  • Hydroxysteroid Dehydrogenases / genetics*
  • Hydroxysteroid Dehydrogenases / metabolism
  • Mice
  • Neovascularization, Physiologic / drug effects
  • Oxidation-Reduction

Substances

  • Hydroxyeicosatetraenoic Acids
  • Arachidonic Acid
  • 19-hydroxy-5,8,11,14-eicosatetraenoic acid
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
  • Cytochrome P-450 Enzyme System
  • Hydroxysteroid Dehydrogenases
  • 3(17)-hydroxysteroid dehydrogenase