title: Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua.
abstract: An important group of antimalarial drugs consists of the endoperoxide sesquiterpene lactone artemisinin and its derivatives. Only little is known about the biosynthesis of artemisinin in Artemisia annua L., particularly about the early enzymatic steps between amorpha-4,11-diene and dihydroartemisinic acid. Analyses of the terpenoids from A. annua leaves and gland secretory cells revealed the presence of the oxygenated amorpha-4,11-diene derivatives artemisinic alcohol, dihydroartemisinic alcohol, artemisinic aldehyde, dihydroartemisinic aldehyde and dihydroartemisinic acid. We also demonstrated the presence of a number of biosynthetic enzymes such as the amorpha-4,11-diene synthase and the--so far unknown--amorpha-4,11-diene hydroxylase as well as artemisinic alcohol and dihydroartemisinic aldehyde dehydrogenase activities in both leaves and glandular trichomes. From these results, we hypothesise that the early steps in artemisinin biosynthesis involve amorpha-4,11-diene hydroxylation to artemisinic alcohol, followed by oxidation to artemisinic aldehyde, reduction of the C11-C13 double bond to dihydroartemisinic aldehyde and oxidation to dihydroartemisinic acid.
authors.affiliation: Plant Research International, Wageningen, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Bertea
authors.forename: J R
authors.initials: JR
authors.lastname: Freije
authors.forename: H
authors.initials: H
authors.lastname: van der Woude
authors.forename: F W
authors.initials: FW
authors.lastname: Verstappen
authors.forename: L
authors.initials: L
authors.lastname: Perk
authors.forename: V
authors.initials: V
authors.lastname: Marquez
authors.forename: J-W
authors.initials: JW
authors.lastname: De Kraker
authors.forename: M A
authors.initials: MA
authors.lastname: Posthumus
authors.forename: B J
authors.initials: BJ
authors.lastname: Jansen
authors.forename: Ae
authors.initials: A
authors.lastname: de Groot
authors.forename: M C
authors.initials: MC
authors.lastname: Franssen
authors.forename: H J
authors.initials: HJ
authors.lastname: Bouwmeester
mesh_terms: D000962:Antimalarials / Q000378:metabolism*; D031172:Artemisia annua / Q000201:enzymology / Q000378:metabolism*; D037621:Artemisinins / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008517:Phytotherapy; D018515:Plant Leaves / Q000201:enzymology / Q000378:metabolism
chemical_list: D000962:Antimalarials; D037621:Artemisinins