Planta

, Volume 212, Issue 3, pp 460–465

Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin

  • T. Eelco Wallaart
  • Harro J. Bouwmeester
  • Jacques Hille
  • Lucas Poppinga
  • Niels C. A. Maijers

DOI: 10.1007/s004250000428

Cite this article as:
Wallaart, T., Bouwmeester, H., Hille, J. et al. Planta (2001) 212: 460. doi:10.1007/s004250000428

Abstract.

The sesquiterpenoid artemisinin, isolated from the plant Artemisia annua L., and its semi-synthetic derivatives are a new and very effective group of antimalarial drugs. A branch point in the biosynthesis of this compound is the cyclisation of the ubiquitous precursor farnesyl diphosphate into the first specific precursor of artemisinin, namely amorpha-4,11-diene. Here we describe the isolation of a cDNA clone encoding amorpha-4,11-diene synthase. The deduced amino acid sequence exhibits the highest identity (50%) with a putative sesquiterpene cyclase of A. annua. When expressed in Escherichia coli, the recombinant enzyme catalyses the formation of amorpha-4,11-diene from farnesyl diphosphate. Introduction of the gene into tobacco (Nicotiana tabacum L.) resulted in the expression of an active enzyme and the accumulation of amorpha-4,11-diene ranging from 0.2 to 1.7 ng per g fresh weight.

Key words:ArtemisiaArtemisininAntimalarial drugAmorpha-411-diene synthase

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • T. Eelco Wallaart
    • 1
  • Harro J. Bouwmeester
    • 2
  • Jacques Hille
    • 3
  • Lucas Poppinga
    • 1
  • Niels C. A. Maijers
    • 1
  1. 1.GenoClipp biotechnology B.V., Meditech Center, L.J. Zielstraweg 1, 9713 GX Groningen, The NetherlandsNL
  2. 2.Plant Research International, P.O. Box 16, 6700 AA Wageningen, The NetherlandsNL
  3. 3.Department Molecular Biology of Plants, University of Groningen, Kerklaan 30, 9751 NN Haren, The NetherlandsNL