Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin
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The sesquiterpenoid artemisinin, isolated these 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.
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cDNAs encoding ADS from A. annua have been isolated, sequenced, and expressed.
“cDNAs encoding ADS from A. annua have been isolated, sequenced, and expressed [293,294].”
From The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao) (2010) · cites this paper as [293]
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References 31 · Cited by 242
- Authors
- Wallaart, T. E., Bouwmeester, H. J., Hille, J., Poppinga, L., & Maijers, N. C. A.
- Affiliations
- University of Groningen (NL)
- Venue
- Planta
- Published
- 2001-02-19
- Volume
- 212
- Issue
- 3
- Pages
- 460-465
- ISSN
- 0032-0935 (ISSN-L)
- 1432-2048
- OpenAlex
- W2108488573
- Cited by
- 242
- References
- 31
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 12 · 2016: 15 · 2015: 11 · 2014: 13 · 2013: 14 · 2012: 23
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- green
- research.wur.nl
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Planta (publishedVersion)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Sesquiterpenes and Asteraceae Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant tissue culture and regeneration
- Keywords
- amorpha-4,11-diene synthase, artemisinin biosynthesis, sesquiterpene cyclase, Artemisia annua, cDNA cloning, recombinant enzyme expression, transgenic tobacco, antimalarial drugs, sesquiterpenes
- MeSH terms
- Amino Acid Sequence, Antimalarials, Base Sequence, Cells, Cultured, Cloning, Molecular, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Gas Chromatography-Mass Spectrometry, Molecular Sequence Data, Plants, Medicinal, Plants, Toxic, RNA, Sesquiterpenes, Nicotiana, Gene Expression, Polymerase Chain Reaction, DNA, Complementary, Artemisia, Alkyl and Aryl Transferases, Artemisinins
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