RESUMEN
Artemisia annua L. produces the sesquiterpene lactone, artemisinin, a potent antimalarial drug that is also effective in treating other parasitic diseases, some viral infections and various neoplasms. Artemisinin is also an allelopathic herbicide that can inhibit the growth of other plants. Unfortunately, the compound is in short supply and thus, studies on its production in the plant are of interest as are low cost methods for drug delivery. Here we review our recent studies on artemisinin production in A. annua during development of the plant as it moves from the vegetative to reproductive stage (flower budding and full flower formation), in response to sugars, and in concert with the production of the ROS, hydrogen peroxide. We also provide new data from animal experiments that measured the potential of using the dried plant directly as a therapeutic. Together these results provide a synopsis of a more global view of regulation of artemisinin biosynthesis in A. annua than previously available. We further suggest an alternative low cost method of drug delivery to treat malaria and other neglected tropical diseases.
RESUMEN
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.