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

TE Wallaart*, HJ Bouwmeester, J Hille, L Poppinga, NCA Maijers, Harro J. Bouwmeester, Niels C.A. Maijers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)460-465
Number of pages6
JournalPlanta
Volume212
Issue number3
DOIs
Publication statusPublished - Feb-2001

Keywords

  • artemisia
  • artemisinin
  • antimalarial drug
  • amorpha-4,11-diene synthase
  • SESQUITERPENE CYCLASE GENE
  • BACTERIAL EXPRESSION
  • DIHYDROARTEMISINIC ACID
  • PLANT TRANSFORMATION
  • TERPENE CYCLASES
  • CDNA ISOLATION
  • ANNUA
  • MONOTERPENE
  • VECTORS
  • TOBACCO

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