Identification of Intermediates and Enzymes Involved in the Early Steps of Artemisinin Biosynthesis in Artemisia annua

C. M. Bertea; J. R. Freije; H. van der Woude; F. W. A. Verstappen; L. Perk; V. Marquez; J.-W. De Kraker; M. A. Posthumus; B. J. M. Jansen; Ae de Groot; M. C. R. Franssen; H. J. Bouwmeester

doi:10.1055/s-2005-837749

Planta Medica, Inhaltsverzeichnis

Planta Med 2005; 71(1): 40-47
DOI: 10.1055/s-2005-837749

Original Paper

Physiology, in vitro Biotechnology
© Georg Thieme Verlag KG Stuttgart · New York

Identification of Intermediates and Enzymes Involved in the Early Steps of Artemisinin Biosynthesis in Artemisia annua

C. M. Bertea¹ ^, ³ , J. R. Freije¹ ^, ² , H. van der Woude¹ ^, ² , F. W. A. Verstappen¹ , L. Perk¹ ^, ² , V. Marquez¹ ^, ² , J-W. De Kraker¹ ^, ² ^, ⁴ , M. A. Posthumus² , B. J. M. Jansen² , Ae. de Groot² , M. C. R. Franssen² , H. J. Bouwmeester¹

¹Plant Research International, Wageningen, The Netherlands
²Laboratory of Organic Chemistry, Wageningen University, Wageningen, The Netherlands
³Current address: Plant Biology Department and Centre of Excellence CEBIOVEM, University of Turin, Turin, Italy
⁴Current address: Max-Planck Institute for Chemical Ecology, Beutenberg Campus, Jena, Germany

Abstract

An important group of antimalarial drugs consists of the endoperoxide sesquiterpene lactone artemisinin and its derivatives. Only little is known about the biosynthesis of artemisinin in Artemisia annua L., particularly about the early enzymatic steps between amorpha-4,11-diene and dihydroartemisinic acid. Analyses of the terpenoids from A. annua leaves and gland secretory cells revealed the presence of the oxygenated amorpha-4,11-diene derivatives artemisinic alcohol, dihydroartemisinic alcohol, artemisinic aldehyde, dihydroartemisinic aldehyde and dihydroartemisinic acid. We also demonstrated the presence of a number of biosynthetic enzymes such as the amorpha-4,11-diene synthase and the - so far unknown - amorpha-4,11-diene hydroxylase as well as artemisinic alcohol and dihydroartemisinic aldehyde dehydrogenase activities in both leaves and glandular trichomes. From these results, we hypothesise that the early steps in artemisinin biosynthesis involve amorpha-4,11-diene hydroxylation to artemisinic alcohol, followed by oxidation to artemisinic aldehyde, reduction of the C11-C13 double bond to dihydroartemisinic aldehyde and oxidation to dihydroartemisinic acid.

Key words

Artemisia annua - Asteraceae - artemisinin - glandular trichomes - biosynthetic pathway - sesquiterpenoids

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References

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