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Identification of Intermediates and Enzymes Involved in the Early Steps of Artemisinin Biosynthesis in Artemisia annua
Open accessAbstract
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.
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“Collectively, these metabolites suggested the presence of two interlinked pathways for the conversion of amorpha-4,11-diene (451) to either dihydroartemisinic acid (480) or artemisinic acid (473), as is shown in Scheme 11 [135].”
From The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao) (2010) · cites this paper as [135]
In the citing paper
“Interestingly, there is now some evidence for such a route to dihydroartemisinic acid (480), which involves two oxidations at C-12 of amorpha-4,11-diene (451), producing artemisinic aldehyde (460) via artemisinic alcohol (458); followed by reduction of the Δ11,13 double bond in (460) to dihydroartemisinic aldehyde (483); and, finally, oxidation of (483) at C-12 to yield dihydroartemisinic acid (”
From The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao) (2010) · cites this paper as [135]
In the citing paper
“In 2005, artemisinic alcohol (458), artemisinic aldehyde (460), dihydroartemisinic alcohol (482) and dihydroartemisinic aldehyde (483) were all isolated as natural products from A. annua [135].”
From The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao) (2010) · cites this paper as [135]
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Metadata
- Authors
- Bertea, C. M., Freije, J. R., van der Woude, H., Verstappen, F. W., Perk, L., Marquez, V., De Kraker, J.-W., Posthumus, M. A., Jansen, B. J., de Groot, A., Franssen, M. C., & Bouwmeester, H. J.
- Affiliations
- Wageningen University & Research (NL)
- Venue
- Planta Medica
- Publisher
- Georg Thieme Verlag KG
- Published
- 2005-01
- Volume
- 71
- Issue
- 1
- Pages
- 40-47
- ISSN
- 0032-0943 (ISSN-L)
- 1439-0221
- OpenAlex
- W2061459669
- Cited by
- 205
- References
- 13
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 9 · 2015: 5 · 2014: 11 · 2013: 14 · 2012: 21
- FWCI
- 5.77
- Type
- journal article
- Language
- de
- Open access
- bronze
- doi.org
- Locations
- Planta Medica (publishedVersion)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Physical Sciences › Chemistry › Organic Chemistry › Sesquiterpenes and Asteraceae Studies
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant tissue culture and regeneration
- Keywords
- artemisinin biosynthesis, Artemisia annua, dihydroartemisinic acid, amorpha-4,11-diene synthase, sesquiterpene lactones, glandular trichomes, antimalarial drugs
- MeSH terms
- Antimalarials, Humans, Gas Chromatography-Mass Spectrometry, Phytotherapy, Plant Leaves, Artemisia annua, Artemisinins
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