Making artemisinin

Covello, Patrick S.

doi:10.1016/j.phytochem.2008.10.001

Cited by 127Plant biochemistry and biosynthesisSesquiterpenes and Asteraceae StudiesPlant tissue culture and regeneration

Making artemisinin

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Covello, Patrick S.·2008·Phytochemistry

DOI 10.1016/j.phytochem.2008.10.001

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Abstract

The possibilities for the production of the antimalarial artemisinin by biological and chemical means are explored. These include native biosynthesis, genetic modification of Artemisia annua and other plants, engineering of microbes, total and partial chemical synthesis and combinations of the above.

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The chemistry of undifferentiated callus and suspension cultures of A. annua seems dominated by sterols and phenylpropanoids that are also found in significant quantities in the parent plants.
“Instead, the chemistry of undifferentiated callus and suspension cultures of A. annua seems to be dominated by sterols, such as stigmasterol (570) and sitosterol (568) (Section 2.7.2) [86,313]; as well as phenylpropanoids, such as scopoletin (184) (Section 2.3; Table 17), all of which are also found in significant quantities in the parent plants [86,313].”
From The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao) (2010) · cites this paper as [313]

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Li, Y.,Huang, H., Wu, Y.-L., 2006, qinghaosu (artemisinin) - a fantastic antimalarial drug from a traditional Chinese medicine. In: Liang, X.-T., Fang, W.-S. (Eds.), Medicinal Chemistry of Bioactive Natural Products Wiley Interscience, Hoboken, pp. 183-256.
Willcox, M., Bodeker, G., Bourdy, G., Dhingra, V., Falquet, J., Ferreira, J.F.S., Graz, B., Hirt, H.-M., Hsu, E., Melillo de Magalhaes, P., Provendier, D., Wright, C.W., 2004. Artemisia annua as a traditional herbal antimalarial. In: Willcox, M., Bodeker, G., Rasoanaivo, P. (Eds.), Traditional Medicinal Plants and Malaria CRC Press, Boca Raton, pp. 43-59.

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Metabolic engineering of plants for artemisinin synthesis
Farhi, M., Kozin, M., Duchin, S., & Vainstein, A. (2013) · Biotechnology and Genetic Engineering Reviews · doi:10.1080/02648725.2013.821283 · Cited by 23 · see citing works
“The subsequent biochemical steps are not yet clear, but it has been suggested that dihydroartemisinic aldehyde oxidation, catalyzed by aldehyde dehydrogenase 1 (ALDH1), leads to the formation of dihydroartemisinic acid (Figure 1) (Covello, 2008; Ro et al., 2006; Teoh, Polichuk, Reed, & Covello, 2006; Teoh, Polichuk, R…”
Background
Increases in leaf artemisinin concentration in Artemisia annua in response to the application of phosphorus and boron
Davies, M. J., Atkinson, C. J., Burns, C., Arroo, R., & Woolley, J. (2011) · Industrial Crops and Products · doi:10.1016/j.indcrop.2011.05.002 · Cited by 23 · see citing works
Identification of Putative Artemisia annua ABCG Transporter Unigenes Related to Artemisinin Yield Following Expression Analysis in Different Plant Tissues and in Response to Methyl Jasmonate and Abscisic Acid Treatments
Zhang, L., Lu, X., Shen, Q., Chen, Y., Wang, T., Zhang, F., Wu, S., Jiang, W., Liu, P., Zhang, L., et al. (2011) · Plant Molecular Biology Reporter · doi:10.1007/s11105-011-0400-8 · Cited by 22 · see citing works
Sesquiterpene lactone engineering in microbial and plant platforms: parthenolide and artemisinin as case studies
Majdi, M., Ashengroph, M., & Abdollahi, M. R. (2015) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-015-7128-6 · Cited by 22 · see citing works
“probably non-enzymatic, which requires light and molecular oxygen (Covello 2008).”
Background
Chemical defense against insects in Heterotheca subaxillaris and three Orobanchaceae species using exudates from trichomes
Morimoto, M. (2019) · Pest Management Science · doi:10.1002/ps.5395 · Cited by 22 · see citing works
Sesquiterpenes
Chappell, J., & Coates, R. M. (2010) · Elsevier eBooks · doi:10.1016/b978-008045382-8.00005-8 · Cited by 24 · see citing works
A phylogenetic perspective of antiviral species of the genus Artemisia (Asteraceae-Anthemideae): A proposal of anti SARS-CoV-2 (COVID-19) candidate taxa
Hussain, A. (2022) · Journal of Herbal Medicine · doi:10.1016/j.hermed.2022.100601 · Cited by 19 · see citing works
“Artemisinin is a sesquiterpenoid lactone present in the extracts of different Artemisia species, including A. annua (Covello, 2008; Ikram and Simonsen, 2017; Pellicer et al., 2018; Nganthoi and Sanatombi, 2019) A. apiacea, A. macrocephala and A. thuscula (Pellicer et al., 2018), with 1, 2,…”
Wild Egyptian medicinal plants show in vitro and in vivo cytotoxicity and antimalarial activities
Abdou, A. M., Seddek, A., Abdelmageed, N., et al. (2022) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-022-03566-5 · Cited by 16 · see citing works
A regulated synthetic operon facilitates stable overexpression of multigene terpenoid pathway in Bacillus subtilis
Abdallah, I. I., Xue, D., Pramastya, H., et al. (2020) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-019-02257-4 · Cited by 16 · see citing works
Artemisinin content and DNA profiling of Artemisia species of Manipur
Nganthoi, M., & Sanatombi, K. (2019) · South African Journal of Botany · doi:10.1016/j.sajb.2019.06.027 · Cited by 16 · see citing works
Nonclassical CH−π Supramolecular Interactions in Artemisinic Acid Favor a Single Conformation, Yielding High Diastereoselectivity in the Reduction with Diazene
CASTRO, B., Chaudret, R., Ricci, G., Kurz, M. E., Ochsenbein, P., Kretzschmar, G., Kraft, V., Rossen, K., & Eisenstein, O. (2014) · The Journal of Organic Chemistry · doi:10.1021/jo500233z · Cited by 15 · see citing works
Synthesis of the artemisinin‐imprinting polymers on silica surface and its adsorption behavior in supercritical CO2 fluid
Yang, B., & Cao, X. (2011) · AIChE Journal · doi:10.1002/aic.12547 · Cited by 15 · see citing works
Metabolic analyses elucidate non-trivial gene targets for amplifying dihydroartemisinic acid production in yeast
Misra, A., Conway, M. F., Johnnie, J., Qureshi, T. M., Lige, B., Derrick, A. M., Agbo, E. C., & Sriram, G. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00200 · Cited by 14 · see citing works
““fmicb-04-00200” — 2013/7/24 — 20:28 — page 1 — #1 ORIGINAL RESEARCH ARTICLE published: 26 July 2013 doi: 10.3389/fmicb.2013.00200 Metabolic analyses elucidate non-trivial gene targets for amplifying dihydroartemisinic acid production in yeast”
BackgroundInfluential
AaWRKY4 upregulates artemisinin content through boosting the expressions of key enzymes in artemisinin biosynthetic pathway
Huang, H., Xing, S., Tang, K., & Jiang, W. (2021) · Plant Cell Tissue and Organ Culture (PCTOC) · doi:10.1007/s11240-021-02049-8 · Cited by 14 · see citing works
“2002; Covello 2008).”
Background
Optimization of Ultrasound-Assisted Extraction of Artemisinin fromArtemisia annuaL. by Response Surface Methodology
Zhang, H., Zhang, L. R., Hu, X., Zhou, Y., Ding, C., Yang, R., Wang, X., & Li, D. (2013) · Separation Science and Technology · doi:10.1080/01496395.2013.862545 · Cited by 13 · see citing works
Asymmetric Bio‐epoxidation of Unactivated Alkenes
Li, J., Gu, W., Wang, Z., et al. (2023) · ChemBioChem · doi:10.1002/cbic.202200719 · Cited by 13 · see citing works
Singlet oxygen as a signaling transducer for modulating artemisinin biosynthetic genes in Artemisia annua
Zeng, Q. P., Zeng, X.-M., Yang, R., & Yang, X. (2011) · Biologia Plantarum · doi:10.1007/s10535-011-0166-8 · Cited by 12 · see citing works
“Following catalysis by Δ11(13)-doublebond reductase 2 (DBR2), artemisinic aldehyde is reduced to dihydroartemisinic aldehyde, which is then oxidized to dihydroartemisinic acid (DHAA) by a trichome-specific aldehyde dehydrogenase, ALDH1 (Covello 2008).”
BackgroundInfluential
STUDY OF EFFECT OF EXTRACTION CONDITIONS ON THE BIOCHEMICAL COMPOSITION AND ANTIOXIDANT ACTIVITY OF ARTEMISIA ABSINTHIUM BY HPLC AND TLC
Ghafouri, H., Sariri, R., & Naghavi, M. R. (2013) · Journal of Liquid Chromatography & Related Technologies · doi:10.1080/10826076.2013.803200 · Cited by 12 · see citing works
“Artemisinin is a sesquiterpenoid produced in glandular trichomes of Artemisia annua.([16]) Other species of Artemisia have been screened as potential new sources for agricultural production.”
Background
Antimalarial and Antileishmanial Activities of Phytophenolics and Their Synthetic Analogues
Morimoto, M., Cantrell, C. L., Khan, S. I., et al. (2017) · Chemistry & Biodiversity · doi:10.1002/cbdv.201700324 · Cited by 12 · see citing works
Unravelling the Impact of Essential Mineral Nutrients on Active Constituents of Selected Medicinal and Aromatic Plants
Singh, M., Ali, A. A., & Qureshi, M. I. (2017) · Springer eBooks · doi:10.1007/978-3-319-58841-4_9 · Cited by 12 · see citing works
Root regulation of artemisinin production in Artemisia annua: trichome and metabolite evidence
Wang, S., Towler, M. J., & Weathers, P. J. (2016) · Planta · doi:10.1007/s00425-016-2560-0 · Cited by 9 · see citing works
Socioeconomic Values of Herbal Medicine
Odubo, T. C., Iyiola, A. O., Adetola, B. O., Kolawole, A. S., Izah, S. C., Raimi, M. O., & Ogwu, M. C. (2024) · Reference series in phytochemistry · doi:10.1007/978-3-031-43199-9_3 · Cited by 12 · see citing works
Using β-ocimene to increase the artemisinin content in juvenile plants of Artemisia annua L.
Xiao, M., Liu, R., Long, C., Ruan, Y., & Liu, C. (2020) · Biotechnology Letters · doi:10.1007/s10529-020-02849-6 · Cited by 9 · see citing works
“Currently, it is understood that the precursors for artemisinin biosynthesis originate from the cytosolic mevalonic acid (MVP) pathway and methylerythritol phosphate (MEP) pathway (Covello 2008; Ma et al. 2015).”
Background
New Medical Applications of Plant Secondary Metabolites
Heilmann, J. (2010) · Wiley-Blackwell eBooks · doi:10.1002/9781444318876.ch5 · Cited by 10 · see citing works
Terpenoid Biosynthesis
Ro, D. (2011) · Wiley eBooks · doi:10.1002/9781119991311.ch8 · Cited by 11 · see citing works
Inducing Effect of Dihydroartemisinic Acid in the Biosynthesis of Artemisinins with Cultured Cells ofArtemisia annuaby Enhancing the Expression of Genes
Zhu, J., Yang, J., Zeng, Z., Zhang, W., Song, L., Wen, W., & Yu, R. (2014) · The Scientific World JOURNAL · doi:10.1155/2014/293190 · Cited by 8 · see citing works
Yeast Synthetic Biology for Production of Artemisinin as an Antimalarial Drug
Kashkooli, A. B., Kalalagh, K. F., & Babaei, A. (2022) · Springer eBooks · doi:10.1007/978-3-030-89680-5_6 · Cited by 7 · see citing works
Medicinal Plants: Guests and Hosts in the Heterologous Expression of High-Value Products
Vasilev, N. P. (2021) · Planta Medica · doi:10.1055/a-1576-4148 · Cited by 6 · see citing works
Socioeconomic Values of Herbal Medicine
Odubo, T. C., Iyiola, A. O., Adetola, B. O., Kolawole, A. S., Izah, S. C., Raimi, M. O., & Ogwu, M. C. (2023) · Reference series in phytochemistry · doi:10.1007/978-3-031-21973-3_3-1 · Cited by 6 · see citing works
Recent Trends on Production Sources, Biosynthesis Pathways and Antiviral Efficacies of Artemisinin: A Candidate Phytomedicine against SARS-CoV-2
Hussain, A. (2023) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201024666230327082051 · Cited by 6 · see citing works

Is Artemisinin the Only Antiplasmodial Compound in the Artemisia annua Tea Infusion? An in Vitro Study
Mouton, J., Jansen, O., Frédérich, M., & van der Kooy, F. (2013) · Planta Medica · doi:10.1055/s-0032-1328324 · Cited by 20 · see citing works
Artemisia annua glandular secretory trichomes： the biofactory of antimalarial agent artemisinin
Ling, Xiao, X., Hexin, et al. (2016) · 中国科学通报：英文版
A review of various efforts to increase artemisinin and other antimalarial compounds in Artemisia Annua L plant
Aidah, N., Bazira, J., Tolo, C. U., & Engeu, P. O. (2018) · Cogent Biology · doi:10.1080/23312025.2018.1513312 · Cited by 16 · see citing works
Self-immobilized aggreage culture of Artemisia annua L. for imroved artemisinin
Hu, F., Chen, C.-L., & Guanlin, W. (2003) · Zhiwu yanjiu
Metabolic engineering of artemisinin biosynthesis in Artemisia annua L.
Liu, B., Wang, H., Du, Z., Li, G., & Ye, H. (2010) · Plant Cell Reports · doi:10.1007/s00299-010-0967-9 · Cited by 82 · see citing works

Authors: Covello, P. S.
Affiliations: Plant Biotechnology Institute (CA)
Corresponding author: Covello, Patrick S.
Venue: Phytochemistry
Publisher: Elsevier BV
Published: 2008-12
Volume: 69
Issue: 17
Pages: 2881-2885
ISSN: 0031-9422 (ISSN-L)
DOI: 10.1016/j.phytochem.2008.10.001
OpenAlex: W4236404432
Cited by: 127
References: 0
Citations by year: 2026: 1 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 8 · 2016: 14 · 2015: 8 · 2014: 6 · 2013: 13 · 2012: 9
FWCI: 5.33
Type: journal article
Language: en
Open access: green
nrc-publications.canada.ca
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Phytochemistry (publishedVersion)
PubMed (publishedVersion)
NPARC (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: artemisinin, antimalarial drugs, Artemisia annua, biosynthesis, genetic modification, microbial engineering, total synthesis, semisynthesis, drug production
MeSH terms: Escherichia coli, Genetic Engineering, Molecular Structure, Artemisia, Artemisinins

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