Elucidation and in planta reconstitution of the parthenolide biosynthetic pathway
2014
Authors:
Liu, QingManzano, David
Tanić, Nikola
Pešić, Milica
Banković, Jasna Z.
Pateraki, Irini
Ricard, Lea
Ferrer, Albert
de Vos, Ric
van de Krol, Sander
Bouwmeester, Harro
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
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 1.4 mu g g(-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 3
beta-hydroxylase was identified opening up further options to improve
the water solubility of parthenolide and therefore its potential as a
drug. (C) 2014 International Metabolic Engineering Society. Published by
Elsevier Inc. All rights reserved.
Keywords:
Parthenolide; Biosynthetic pathway reconstitution; Feverfew; Metabolic engineeringSource:
Metabolic Engineering, 2014, 23, 145-153
DOI: 10.1016/j.ymben.2014.03.005
ISSN: 1096-7184