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Elucidation and in planta reconstitution of the parthenolide biosynthetic pathway
dc.creator | Liu, Qing | |
dc.creator | Manzano, David | |
dc.creator | Tanić, Nikola | |
dc.creator | Pešić, Milica | |
dc.creator | Banković, Jasna Z. | |
dc.creator | Pateraki, Irini | |
dc.creator | Ricard, Lea | |
dc.creator | Ferrer, Albert | |
dc.creator | de Vos, Ric | |
dc.creator | van de Krol, Sander | |
dc.creator | Bouwmeester, Harro | |
dc.date.accessioned | 2016-05-23T11:00:34Z | |
dc.date.issued | 2014 | |
dc.identifier.issn | 1096-7184 | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/2218 | |
dc.description.abstract | 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. | en |
dc.description.sponsorship | European Commission (EU) {[}227448]; Netherlands Metabolomics Centre as part of the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research; Centre for BioSystems Genomics as part of the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research | en |
dc.language | English | |
dc.rights | restrictedAccess | |
dc.source | Metabolic Engineering | |
dc.subject | Parthenolide | |
dc.subject | Biosynthetic pathway reconstitution | |
dc.subject | Feverfew | |
dc.subject | Metabolic engineering | |
dc.title | Elucidation and in planta reconstitution of the parthenolide biosynthetic pathway | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Таниц, Никола; Песиц, Милица; Патераки, Ирини; Боуwмеестер, Харро; Банковић, Јасна З.; Феррер, Aлберт; де Вос, Риц; Манзано, Давид; Лиу, Qинг; Рицард, Леа; ван де Крол, Сандер; | |
dc.citation.volume | 23 | |
dc.identifier.doi | 10.1016/j.ymben.2014.03.005 | |
dc.identifier.scopus | 2-s2.0-84898867034 | |
dc.identifier.wos | 000335385500015 | |
dc.citation.spage | 145 | |
dc.citation.epage | 153 | |
dc.type.version | publishedVersion | en |
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