title: The molecular cloning of dihydroartemisinic aldehyde reductase and its implication in artemisinin biosynthesis in Artemisia annua.
abstract: A key point in the biosynthesis of the antimalarial drug artemisinin is the formation of dihydroartemisinic aldehyde which represents the key difference between chemotype specific pathways. This key intermediate is the substrate for several competing enzymes, some of which increase the metabolic flux towards artemisinin, and some of which--as we show in the present study--may have a negative impact on artemisinin production. In an effort to understand the biosynthetic network of artemisinin biosynthesis, extracts of A. annua flowers were investigated and found to contain an enzyme activity competing in a negative sense with artemisinin biosynthesis. The enzyme Red1 is a broad substrate oxidoreductase belonging to the short chain dehydrogenase/reductase family with high affinity for dihydroartemisinic aldehyde and valuable monoterpenoids. Spatial and temporal analysis of cDNA revealed Red1 to be trichome specific. The relevance of Red1 to artemisinin biosynthesis is discussed.
authors.affiliation: Pharmaceutical Biology, University of Groningen, Groningen, The Netherlands.
authors.forename: Anna-Margareta
authors.initials: AM
authors.lastname: Rydén
authors.forename: Carolien
authors.initials: C
authors.lastname: Ruyter-Spira
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Quax
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.forename: Toshiya
authors.initials: T
authors.lastname: Muranaka
authors.forename: Oliver
authors.initials: O
authors.lastname: Kayser
authors.forename: Harro
authors.initials: H
authors.lastname: Bouwmeester
mesh_terms: D000449:Aldehyde Reductase / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D031172:Artemisia annua / Q000201:enzymology* / Q000235:genetics; D037621:Artemisinins / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D020224:Expressed Sequence Tags; D035264:Flowers / Q000201:enzymology / Q000235:genetics; D008401:Gas Chromatography-Mass Spectrometry; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics*; D020539:Sequence Analysis, Protein
chemical_list: D037621:Artemisinins; D018076:DNA, Complementary; D010940:Plant Proteins; C031327:artemisinin; D000449:Aldehyde Reductase