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
来源：
PHYTOCHEMISTRY | 2007年 / 68卷 / 14期
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
相关论文
共 53 条
  • [1] Artemisinin, a novel antimalarial drug: Biochemical and molecular approaches for enhanced production
    Abdin, MZ
    Israr, M
    Rehman, RU
    Jain, SK
    [J]. PLANTA MEDICA, 2003, 69 (04) : 289 - 299
  • [2] Biosynthesis of the isoprene units of chamomile sesquiterpenes
    Adam, KP
    Zapp, J
    [J]. PHYTOCHEMISTRY, 1998, 48 (06) : 953 - 959
  • [3] BIOSYNTHESIS OF ARTEMISININ IN ARTEMISIA-ANNUA
    AKHILA, A
    THAKUR, RS
    POPLI, SP
    [J]. PHYTOCHEMISTRY, 1987, 26 (07) : 1927 - 1930
  • [4] [Anonymous], MED CHEM BIOACTIVE N, DOI DOI 10.1002/0471739340.CH5
  • [5] AOYAMA Y, 1989, J BIOL CHEM, V264, P18502
  • [6] Isoprenoid biosynthesis in Artemisia annua:: Cloning and heterologous expression of a germacrene A synthase from a glandular trichome cDNA library
    Bertea, Cinzia M.
    Voster, Alessandra
    Verstappen, Francel W. A.
    Maffei, Massimo
    Beekwilder, Jules
    Bouwmeester, Harro J.
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2006, 448 (1-2) : 3 - 12
  • [7] Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua
    Bertea, CM
    Freije, JR
    van der Woude, H
    Verstappen, FWA
    Perk, L
    Marquez, V
    De Kraker, JW
    Posthumus, MA
    Jansen, BJM
    de Groot, A
    Franssen, MCR
    Bouwmeester, HJ
    [J]. PLANTA MEDICA, 2005, 71 (01) : 40 - 47
  • [8] Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis
    Bouwmeester, HJ
    Wallaart, TE
    Janssen, MHA
    van Loo, B
    Jansen, BJM
    Posthumus, MA
    Schmidt, CO
    De Kraker, JW
    König, WA
    Franssen, MCR
    [J]. PHYTOCHEMISTRY, 1999, 52 (05) : 843 - 854
  • [9] In vivo transformations of dihydroartemisinic acid in Artemisia annua plants
    Brown, GD
    Sy, LK
    [J]. TETRAHEDRON, 2004, 60 (05) : 1139 - 1159
  • [10] Amorpha-4,11-diene synthase of Artemisia annua:: cDNA isolation and bacterial expression of a terpene synthase involved in artemisinin biosynthesis
    Chang, YJ
    Song, SH
    Park, SH
    Kim, SU
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2000, 383 (02) : 178 - 184
123456