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

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 f...

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Bibliographic Details
Published in:	Planta Vol. 212; no. 3; pp. 460 - 465
Main Authors:	Wallaart, T. Eelco, Bouwmeester, Harro J., Hille, Jacques, Poppinga, Lucas, Maijers, Niels C. A.
Format:	Journal Article
Language:	English
Published:	Berlin Springer-Verlag 01-02-2001 Springer
Subjects:	Agronomy. Soil science and plant productions Alkyl and Aryl Transferases - chemistry Alkyl and Aryl Transferases - genetics Alkyl and Aryl Transferases - metabolism Amino Acid Sequence Amino acids Antimalarials Antimalarials - isolation & purification Artemisia - chemistry Artemisia - genetics Artemisinins Base Sequence Biological and medical sciences Biosynthesis Cells, Cultured Cloning, Molecular Complementary DNA DNA, Complementary - genetics DNA, Complementary - isolation & purification DNA, Complementary - metabolism Economic plant physiology Electrophoresis, Polyacrylamide Gel Enzymes Escherichia coli - enzymology Escherichia coli - genetics Fundamental and applied biological sciences. Psychology Gas Chromatography-Mass Spectrometry Gene Expression Metabolism Molecular Sequence Data Nicotiana - enzymology Nicotiana - genetics Nutrition. Photosynthesis. Respiration. Metabolism Plant physiology and development Plant Research International Plants, Medicinal Plants, Toxic Polymerase Chain Reaction RNA RNA - isolation & purification Sesquiterpenes Sesquiterpenes - isolation & purification Terpenes Drug Antimalarial Nucleotide sequence Artemisinin Biosynthesis Metabolic pathway Compositae Gene expression Nicotiana tabacum Medicinal plant Characterization Dicotyledones Angiospermae Spermatophyta Solanaceae Molecular cloning Aminoacid sequence
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Summary:	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.
ISSN:	0032-0935 1432-2048
DOI:	10.1007/s004250000428