Forskning ved Københavns Universitet - Københavns Universitet

Forside

Elucidation and in planta reconstitution of the parthenolide biosynthetic pathway

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Qing Liu
  • David Manzano
  • Nikola Tanić
  • Milica Pesic
  • Jasna Bankovic
  • Pateraki, Irini
  • Lea Ricard
  • Albert Ferrer
  • Ric de Vos
  • Sander van de Krol
  • Harro Bouwmeester

Parthenolide, the main bioactive compound of the medicinal plant feverfew (Tanacetum parthenium), is a promising anti-cancer drug. However, the biosynthetic pathway of parthenolide has not been elucidated yet. Here we report on the isolation and characterization of all the genes from feverfew that are required for the biosynthesis of parthenolide, using a combination of 454 sequencing of a feverfew glandular trichome cDNA library, co-expression analysis and metabolomics. When parthenolide biosynthesis was reconstituted by transient co-expression of all pathway genes in Nicotiana benthamiana, up to 1.4μgg-1 parthenolide was produced, mostly present as cysteine and glutathione conjugates. These relatively polar conjugates were highly active against colon cancer cells, with only slightly lower activity than free parthenolide. In addition to these biosynthetic genes, another gene encoding a costunolide and parthenolide 3β-hydroxylase was identified opening up further options to improve the water solubility of parthenolide and therefore its potential as a drug.

OriginalsprogEngelsk
TidsskriftMetabolic Engineering
Vol/bind23
Sider (fra-til)145-153
Antal sider9
ISSN1096-7176
DOI
StatusUdgivet - 2014

ID: 131464761