Functional genomics and the biosynthesis of artemisinin

被引:129
|
作者
Covello, Patrick S. [1 ]
Teoh, Keat H. [1 ]
Polichuk, Devin R. [1 ]
Reed, Darwin W. [1 ]
Nowak, Goska [1 ]
机构
[1] Natl Res Council Canada, Inst Plant Biotechnol, Saskatoon, SK S7N 0W9, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
artemisia annua; Asteraceae; artemisinin; sesquiterpene; cytochrome P450; trichome;
D O I
10.1016/j.phytochem.2007.02.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 CYP71 AV1, 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. Crown Copyright (c) 2007 Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1864 / 1871
页数:8
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