Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis

被引:209
作者
Bouwmeester, HJ
Wallaart, TE
Janssen, MHA
van Loo, B
Jansen, BJM
Posthumus, MA
Schmidt, CO
De Kraker, JW
König, WA
Franssen, MCR
机构
[1] DLO, AB, Res Inst Agrobiol & Soil Fertil, NL-6700 AA Wageningen, Netherlands
[2] Univ Groningen, Dept Pharmaceut Biol, Univ Ctr Pharm, NL-9713 AV Groningen, Netherlands
[3] Agr Univ Wageningen, Dept Organ Chem, NL-6703 HB Wageningen, Netherlands
[4] Univ Hamburg, Dept Organ Chem, D-20146 Hamburg, Germany
关键词
Artemisia annua; Asteraceae; biosynthesis; sesquiterpenoids; artemisinin; amorpha-4,11-diene;
D O I
10.1016/S0031-9422(99)00206-X
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
The endoperoxide sesquiterpene lactone artemisinin and its derivatives are a promising new group of drugs against malaria. Artemisinin is a constituent of the annual herb Artemisia annua L. So far only the later steps in artemisinin biosynthesis - from artemisinic acid - have been elucidated and the expected olefinic sesquiterpene intermediate has never been demonstrated. In pentane extracts of A. annua leaves we detected a sesquiterpene with the mass spectrum of amorpha-4,11-diene. Synthesis of amorpha-4,11-diene from artemisinic acid confirmed the identity. In addition we identified several sesquiterpene synthases of which one of the major activities catalysed the formation of amorpha-4,11-diene from farnesyl diphosphate. This enzyme was partially purified and shows the typical characteristics of sesquiterpene syntheses, such as a broad pH optimum around 6.5-7.0, a molecular mass of 56 kDa, and a K-m of 0.6 mu M. The structure and configuration of amorpha-4,11-diene, its low content in A. annua and the high activity of amorpha-4,11-diene synthase all support that amorpha-4,11-diene is the likely olefinic sesquiterpene intermediate in the biosynthesis of artemisinin. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:843 / 854
页数:12
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