Artemisinin biosynthesis in growing plants of Artemisia annua. A ¹³CO₂ study

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• 作者：Nicholas Schramek ; Huahong Wang ; Werner R&#xf6 ; misch-Margl ; Birgit Keil ; Tanja Radykewicz ; Bernhard Winzenh&#xf6 ; rlein ; Ludger Beerhues ; Adelbert Bacher ; Felix Rohdich ; Jonathan Gershenzon ; Benye Liu
• 关键词：Terpene ; Biosynthesis ; Mevalonate ; 1-Deoxyxylulose phosphate ; Artemisinin
• 刊名：Phytochemistry
• 出版年：2010
• 出版时间：February 2010
• 年：2010
• 卷：71
• 期：2-3
• 页码：179-187
• 全文大小：611 K

文摘

Artemisinin from Artemisia annua has become one of the most important drugs for malaria therapy. Its biosynthesis proceeds via amorpha-4,11-diene, but it is still unknown whether the isoprenoid precursors units are obtained by the mevalonate pathway or the more recently discovered non-mevalonate pathway. In order to address that question, a plant of A. annua was grown in an atmosphere containing 700 ppm of ¹³CO₂ for 100 min. Following a chase period of 10 days, artemisinin was isolated and analyzed by ¹³C NMR spectroscopy. The isotopologue pattern shows that artemisinin was predominantly biosynthesized from (E,E)-farnesyl diphosphate (FPP) whose central isoprenoid unit had been obtained via the non-mevalonate pathway. The isotopologue data confirm the previously proposed mechanisms for the cyclization of (E,E)-FPP to amorphadiene and its oxidative conversion to artemisinin. They also support deprotonation of a terminal allyl cation intermediate as the final step in the enzymatic conversion of FPP to amorphadiene and show that either of the two methyl groups can undergo deprotonation.