Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin.
Artemisinin, a sesquiterpene lactone endoperoxide derived from the plant Artemisia annua, forms the basis of the most important treatments of malaria in use today. In an effort to elucidate the biosynthesis of artemisinin, an expressed sequence tag approach to identifying the relevant biosynthetic genes was undertaken using isolated glandular trichomes as a source of mRNA. A cDNA clone encoding a cytochrome P450 designated CYP71AV1 was characterized by expression in Saccharomyces cerevisiae and shown to catalyze the oxidation of the proposed biosynthetic intermediates amorpha-4,11-diene, artemisinic alcohol and artemisinic aldehyde. The identification of the CYP71AV1 gene should allow for the engineering of semi-synthetic production of artemisinin in appropriate plant or microbial hosts.
Teoh
Keat H
KH
Plant Biotechnology Institute, 110 Gymnasium Place, Saskatoon, Sask., Canada S7N OW9.
Polichuk
Devin R
DR
Reed
Darwin W
DW
Nowak
Goska
G
Covello
Patrick S
PS
D000962:Antimalarials / Q000138:chemical synthesis*; D031172:Artemisia annua / Q000166:cytology / Q000201:enzymology*; D037621:Artemisinins / Q000138:chemical synthesis*; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D018076:DNA, Complementary; D018744:DNA, Plant; D004847:Epithelial Cells / Q000201:enzymology; D010084:Oxidation-Reduction; D010940:Plant Proteins / Q000235:genetics* / Q000378:metabolism*; D010946:Plants, Medicinal / Q000166:cytology / Q000201:enzymology; D012717:Sesquiterpenes / Q000138:chemical synthesis*
D000962:Antimalarials; D037621:Artemisinins; D018076:DNA, Complementary; D018744:DNA, Plant; D010940:Plant Proteins; D012717:Sesquiterpenes; D003577:Cytochrome P-450 Enzyme System; C031327:artemisinin