Functional genomics and the biosynthesis of artemisinin.
Artemisinin, a sesquiterpene lactone endoperoxide derived from the glandular secretory trichomes (GSTs) of Artemisia annua, provides the basis for the most effective treatments of malaria. The biology and biochemistry of GSTs of the Asteraceae and their biosynthesis of isoprenoids is reviewed. Recent efforts to understand the biosynthesis of artemisinin in A. annua GSTs are discussed in detail. This includes the development in the authors' laboratory of an expressed sequence tag (EST) approach to identifying the relevant biosynthetic genes using isolated GST as a source of mRNA. This has lead to the isolation of a cDNA encoding CYP71AV1, a multifunctional cytochrome P450 which catalyzes multiple oxidations of the sesquiterpene intermediate amorpha-4,11-diene to artemisinic acid. Further biochemical and molecular genetic work is required to elucidate the precise route from artemisinic alcohol to artemisinin and to engineer more efficient low cost production of artemisinin-based antimalarial drugs.
Covello
Patrick S
PS
Plant Biotechnology Institute, 110 Gymnasium Place, Saskatoon, SK, Canada S7N OW9. Patrick.Covello@nrc-cnrc.gc.ca
Teoh
Keat H
KH
Polichuk
Devin R
DR
Reed
Darwin W
DW
Nowak
Goska
G
D000818:Animals; D037621:Artemisinins / Q000737:chemistry / Q000378:metabolism*; D053898:Biosynthetic Pathways; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D023281:Genomics; D015394:Molecular Structure; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000378:metabolism
D037621:Artemisinins; D018076:DNA, Complementary; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C515348:amorpha-4,11-diene; C031327:artemisinin; D010105:Oxygenases