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

Authors

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

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
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© Springer-Verlag Berlin Heidelberg 2001