2007 Functional genomics and the biosynthesis of artemisinin文档.pdfVIP

PHYTOCHEMISTRY Phytochemistry 68 (2007) 1864–1871 /locate/phytochem Functional genomics and the biosynthesis of artemisinin Patrick S. Covello *, Keat H. Teoh, Devin R. Polichuk, Darwin W. Reed, Goska Nowak Plant Biotechnology Institute, 110 Gymnasium Place, Saskatoon, SK, Canada S7N OW9 Received 30 October 2006; received in revised form 11 January 2007 Available online 30 March 2007 Abstract Artemisinin, a sesquiterpene lactone endoperoxide derived from the glandular secretory trichomes (GSTs) of Artemisia annua, pro- vides the basis for the most effective treatments of malaria. The biology and biochemistry of GSTs of the Asteraceae and their biosyn- thesis 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 bio- synthetic genes using isolated GST as a source of mRNA. This has lead to the isolation of a cDNA encoding CYP71AV1, a multifunc- tional 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. Crown Copyright 2007 Published by Elsevier Ltd. All rights reserved. Keywords: Arte