Elucidation and in planta reconstitution of the parthenolide biosynthetic pathway
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Elucidation and in planta reconstitution of the parthenolide biosynthetic pathway. / Liu, Qing; Manzano, David; Tanić, Nikola; Pesic, Milica; Bankovic, Jasna; Pateraki, Irini; Ricard, Lea; Ferrer, Albert; de Vos, Ric; de Krol, Sander van; Bouwmeester, Harro.
I: Metabolic Engineering, Bind 23, 2014, s. 145-153.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Elucidation and in planta reconstitution of the parthenolide biosynthetic pathway
AU - Liu, Qing
AU - Manzano, David
AU - Tanić, Nikola
AU - Pesic, Milica
AU - Bankovic, Jasna
AU - Pateraki, Irini
AU - Ricard, Lea
AU - Ferrer, Albert
AU - de Vos, Ric
AU - de Krol, Sander van
AU - Bouwmeester, Harro
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Biosynthetic pathway reconstitution
KW - Feverfew
KW - Metabolic engineering
KW - Parthenolide
U2 - 10.1016/j.ymben.2014.03.005
DO - 10.1016/j.ymben.2014.03.005
M3 - Journal article
C2 - 24704560
AN - SCOPUS:84898867034
VL - 23
SP - 145
EP - 153
JO - Metabolic Engineering
JF - Metabolic Engineering
SN - 1096-7176
ER -
ID: 131464761