The Genetics of Artemisinin Content in Artemisia annua L. and the Breeding of High Yielding Cultivars

Delabays, Nicolas; Simonnet, Xavier; Gaudin, Myriam

doi:10.2174/0929867013371635

Cited by 178Genetics and Plant BreedingSesquiterpenes and Asteraceae StudiesGenetic and phenotypic traits in livestock

The Genetics of Artemisinin Content in Artemisia annua L. and the Breeding of High Yielding Cultivars

Delabays, Nicolas, Simonnet, Xavier, Gaudin, Myriam·2001·Current Medicinal Chemistry

DOI 10.2174/0929867013371635

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Abstract

Artemisinin, the endoperoxide sesquiterpene lactone produced by the Chinese medicinal herb Artemisia annua, is very difficult to synthesise. Moreover, its production by mean of cell, tissue or organ cultures is very low. Presently, only its extraction from cultivated plants is viable. A large variation in artemisinin content has been observed in the leaves of plants from different origins. The genetic basis of this variation has been assessed and evidence for a quantitative inheritance of the artemisinin concentration presented. Additive genetic components were predominant, resulting in a high narrow-sense heritability estimate. Thus, goods results can be expected from mass selection for the breeding of lines of Artemisia annua rich in artemisinin. Yet, dominance variance is also present in the total genetic variability, indicating that crosses between selected genotypes should generate progenies with particularly high artemisinin content. As a matter of fact, selection and crossing, in wild populations, of genotypes with high artemisinin concentration resulted in hybrid lines containing up to 1.4 % artemisinin (on dry leaves basis).

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Due to the heterozygous nature of A. annua, not all published plant lines are stable over generations; even transgenic varieties developed in the same laboratory have varying artemisinin content.
“Due to the heterozygous nature of A. annua , however, not all published plant lines are stable over generations; even the transgenic varieties developed in the same laboratory have varying artemisinin content (Delabays et al. 2001).”
From Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches (2021) · cites this paper as Delabays et al. 2001

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Ma, D., Li, G., Alejos-González, F., Zhu, Y., Xue, Z. H., Wang, A., Zhang, H., Li, X., Ye, H., Wang, H., et al. (2017) · The Plant Journal · doi:10.1111/tpj.13583 · Cited by 32 · see citing works
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BackgroundResult
Secondary metabolites of turmeric and ginger on various altitudes and soil characteristics
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Background
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Efferth, T., Banerjee, M., Abu-Darwish, M. S., Abdelfatah, S., Böckers, M., Bhakta-Guha, D., Bolzani, V. D. S., Daak, S., Demirezer, Ö. L., Dawood, M., et al. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.06.007 · Cited by 25 · see citing works
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Background
Genome-wide characterization of B-box gene family in Artemisia annua L. and its potential role in the regulation of artemisinin biosynthesis
He, W., Liu, H., Li, Y., Wu, Z., Xie, Y., Wang, X., Wang, X., Miao, Q., Chen, T., Rahman, S.-U., et al. (2023) · Industrial Crops and Products · doi:10.1016/j.indcrop.2023.116736 · Cited by 25 · see citing works
Genetic engineering of artemisinin biosynthesis: prospects to improve its production
Abdin, M. Z., & Alam, P. (2015) · Acta Physiologiae Plantarum · doi:10.1007/s11738-015-1771-5 · Cited by 25 · see citing works
Effect of Development Stage on the Artemisinin Content and the Sequence Characterized Amplified Region (SCAR) Marker of High‐Artemisinin Yielding Strains of Artemisia annua L.
Zhang, L., Ye, H., & Li, G. (2006) · Journal of Integrative Plant Biology · doi:10.1111/j.1744-7909.2006.00288.x · Cited by 25 · see citing works
A generalist regulator: MYB transcription factors regulate the biosynthesis of active compounds in medicinal plants
Tong, Y., Xue, J., Li, Q., & Zhang, L. (2024) · Journal of Experimental Botany · doi:10.1093/jxb/erae225 · Cited by 25 · see citing works
A Safety Assessment of the Antimalarial Herb Artemisia annua During Pregnancy in Wistar Rats
Abolaji, A. O., Eteng, M. U., Ebong, P. E., Brisibe, E. A., Dar, A., Kabir, N., & Choudhary, M. I. (2012) · Phytotherapy Research · doi:10.1002/ptr.4760 · Cited by 24 · see citing works
Seasonal and Differential Sesquiterpene Accumulation in Artemisia annua Suggest Selection Based on Both Artemisinin and Dihydroartemisinic Acid may Increase Artemisinin in planta
Ferreira, J. F. S., Benedito, V. A., Sandhu, D., Marchese, J. A., & Liu, S. (2018) · Frontiers in Plant Science · doi:10.3389/fpls.2018.01096 · Cited by 25 · see citing works
“This was later confirmed by narrow-sense heritability (Delabays et al., 2001) suggesting that additive effects play a major role in the total genetic variance, and that selection for both ART and DHAA traits will be highly and efficiently conserved, leading to further increase in ART leaf concentration of new hybrids.”
BackgroundResult
Manual de Frascati
y Tecnología, F. E. C. (2010) · La Sociología en sus Escenarios · Cited by 23 · see citing works
Searching for Artemisinin Production Improvement in Plants and Microorganisms
Barbacka, K., & Baer‐Dubowska, W. (2011) · Current Pharmaceutical Biotechnology · doi:10.2174/138920111798376923 · Cited by 22 · see citing works
Iron oxide nanoparticles (Fe3O4-NPs) elicited Artemisia annua L. in vitro, toward enhancing artemisinin production through overexpression of key genes in the terpenoids biosynthetic pathway and induction of oxidative stress
Ayoobi, A., Saboora, A., Asgarani, E., & Efferth, T. (2024) · Plant Cell Tissue and Organ Culture (PCTOC) · doi:10.1007/s11240-024-02705-9 · Cited by 23 · see citing works
“Furthermore, the market places a high demand for artemisinin; hence, there is insufficient supply (Delabays et al. 2001).”
Box–Behnken experimental design for extraction of artemisinin from Artemisia annua and validation of the assay method
Silva, E. D. O., Borges, L. L., da Conceição, E. C., & Bara, M. T. F. (2017) · Revista Brasileira de Farmacognosia · doi:10.1016/j.bjp.2017.03.002 · Cited by 22 · see citing works
“To date an economically viable and safe method of synthesis, capable of substituting extraction from the plant drug, has not been developed (Delabays et al., 2001; Fleming and Freyhold, 2007).”
Method
A golden phoenix arising from the herbal nest — A review and reflection on the study of antimalarial drug Qinghaosu
Li, Y., & Wu, Y. (2010) · Frontiers of Chemistry in China · doi:10.1007/s11458-010-0214-5 · Cited by 20 · see citing works
Flower morphology and floral sequence in Artemisia annua (Asteraceae)1
Wetzstein, H. Y., Porter, J. A., Janick, J., & Ferreira, J. (2014) · American Journal of Botany · doi:10.3732/ajb.1300329 · Cited by 21 · see citing works
“Although artemisinin biosynthesis in progeny of self-pollinated A. annua plants has been reported ( Alejos-Gonzalez et al., 2011 ), studies suggest that the species favors cross-pollination with selfing rates of about only 1% ( Delabays et al., 2001 ).”
Background
Silencing amorpha-4,11-diene synthase Genes in Artemisia annua Leads to FPP Accumulation
Catania, T. M., Branigan, C. A., Stawniak, N., Hodson, J., Harvey, D., Larson, T. R., Czechowski, T., & Graham, I. A. (2018) · Frontiers in Plant Science · doi:10.3389/fpls.2018.00547 · Cited by 20 · see citing works
“The high copy numbers for AMS present in the A. annua cv. Artemis could be linked to its high artemisinin yield, and its success as an elite hybrid for commercial production of artemisinin (Delabays et al., 2001).”
Background
Building a golden triangle for the production and use of artemisinin derivatives against falciparum malaria in Africa
Brisibe, E. A., Uyoh, E. A., Brisibe, F., & Magalhães, P. M. (2008) · AFRICAN JOURNAL OF BIOTECHNOLOGY · doi:10.5897/ajb08.076 · Cited by 20 · see citing works
Screening a diverse collection ofArtemisia annuagermplasm accessions for the antimalarial compound, artemisinin
Cockram, J., Hill, C., Burns, C., Arroo, R. R. J., Woolley, J. G., Flockart, I., Robinson, T., Atkinson, C. J., Davies, M. J., Dungey, N., et al. (2012) · Plant Genetic Resources · doi:10.1017/s1479262112000159 · Cited by 19 · see citing works
“Concentration of ART in surveys of A. annua accessions is known to be predominantly ,1%, with the highest content reported being 1.4% (Woerdenbag et al., 1994; Delabays et al., 2001; Kumar et al., 2004; Khanuja et al., 2005).”
BackgroundInfluential
Extraction of Artemisinin, an Active Antimalarial Phytopharmaceutical from Dried Leaves of Artemisia annua L., Using Microwaves and a Validated HPTLC-Visible Method for Its Quantitative Determination
Misra, H., Mehta, D., Mehta, B. K., & Jain, D. C. (2014) · Chromatography Research International · doi:10.1155/2014/361405 · Cited by 19 · see citing works
Effect of high light intensity on photoinhibition, oxyradicals and artemisinin content in Artemisia annua L.
Poulson, M. E., & Thai, T. (2015) · Photosynthetica · doi:10.1007/s11099-015-0130-5 · Cited by 17 · see citing works
Simple and rapid micro‐scale quantification of artemisinin in living Artemisia annua L. by improved gas chromatography with electron‐capture detection
Liu, S., Tian, N., Li, J., et al. (2009) · Biomedical Chromatography · doi:10.1002/bmc.1230 · Cited by 18 · see citing works
“annua is the only practical source of this valuable drug (Delabays et al., 2001).”
Background
Side Products of Recombinant Amorpha-4,11-diene Synthase and Their Effect on Microbial Artemisinin Production
Huang, J., Li, D., Tian, X., Lin, J., Yang, L., Xu, J.-J., & Fang, X. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c07462 · Cited by 17 · see citing works
Biochemical and Haematological Evaluation of Repeated Dose Exposure of Male Wistar Rats to an Ethanolic Extract of Artemisia annua
Eteng, M. U., Abolaji, A. O., Ebong, P. E., Brisibe, E. A., Dar, A., Kabir, N., & Choudhary, M. I. (2012) · Phytotherapy Research · doi:10.1002/ptr.4758 · Cited by 16 · see citing works
“With breeding techniques, artemisinin yields of 1.4% of the dry weight have been achieved (Delabays et al., 2001).”
BackgroundInfluential
Determination of Artemisinin and Moisture Content of Artemisia Annua L. Dry Powder Using a Hand-Held near Infrared Spectroscopy Device
Camps, C., Toussirot, M., Quennoz, M., et al. (2011) · Journal of Near Infrared Spectroscopy · doi:10.1255/jnirs.927 · Cited by 16 · see citing works
“where xij is the absorbance of the spectrum i (for p data points) measured at wavelength j, x –i is the average value of the absorbance of the uncorrected spectrum and SD is the standard deviation of the spectrum, defined as equation (3):”
BackgroundSelf-citation
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
Efficient Somatic Embryogenesis and Organogenesis of Self-Pollination &lt;i&gt;Artemisia annua&lt;/i&gt; Progeny and Artemisinin Formation in Regenerated Plants
Alejos-Gonzalez, F., Perkins, K., Winston, M. I., & Xie, D.-Y. (2013) · American Journal of Plant Sciences · doi:10.4236/ajps.2013.411274 · Cited by 16 · see citing works
“Over the past many years, breeding efforts have largely increased the yield of artemisinin [11,27] and enhanced the understanding of artemisinin biosynthesis [5,12].”
Chemistry, biosynthesis and biological activity of artemisinin and related natural peroxides
Rydén, A.-M., & Kayser, O. (2007) · Topics in Heterocyclic Chemistry · doi:10.1007/7081_2007_085 · Cited by 16 · see citing works
“Delabays et al. (2001) confirm the broad-sense heritability of artemisinin to be between 0.95 and 1 and that the dominance variance of 0.31 was precent in the experiment.”
BackgroundInfluential
Influence of Genetics on the Secondary Metabolites of Plants
Jadaun, J. S., Yadav, R., Yadav, N., Bansal, S., & Sangwan, N. S. (2023) · Springer eBooks · doi:10.1007/978-3-031-18587-8_12 · Cited by 14 · see citing works
Functional Genomic Approaches to Study and Engineer Secondary Metabolism in Plant Cell Cultures
Terryn, N., MONTAGU, M. V., Inzé, D., & Goossens, A. (2007) · Springer eBooks · doi:10.1007/1-4020-5449-1_21 · Cited by 15 · see citing works
“In the case of Artemisia, it has been shown that the genetic variability linked to artemisinin content can be used to generate improved high-yielding varieties (Delabays et al. 2001); thus, it is likely that genetic factors will be identified that are involved in the low or high artemisinin trait.”
The Beneficial Use of Artemisia annua, Artemisinin, and Other Compounds in Animal Health
Morua, E., Cuyas, L., & Matías‐Hernández, L. (2025) · Animals · doi:10.3390/ani15101359 · Cited by 14 · see citing works
“…medium, and high-artemisinin content varieties); growing conditions (such as soil, climate, and photoperiod); harvest timing (as artemisinin concentrations peak during the flower induction phase); and post-harvest processing of the plant (including drying methods and storage conditions) [189–193].”
Molecular cloning, characterization, and promoter analysis of the isochorismate synthase (AaICS1) gene from Artemisia annua
Wang, L., Zhang, Y., Fu, X., Zhang, T., Ma, J., Zhang, L., Qian, H., Tang, K., Li, S., & Zhao, J. (2017) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1600223 · Cited by 13 · see citing works
“At present, A. annua is the sole commercial source of artemisinin, but the content of artemisinin in its flowers and leaves is just 0.05%–1.00% of the dry weight depending on the species (Duke et al., 1994; Delabays et al., 2001; Abdin et al., 2003; Shen et al., 2012; Patra and Srivastava, 2014).”
BackgroundInfluential
Pitfalls in new artemisinin-containing antimalarial drug development
Jambou, R., Bras, J. L., & Randrianarivelojosia, M. (2010) · Trends in Parasitology · doi:10.1016/j.pt.2010.09.004 · Cited by 13 · see citing works
Analysis of Artemisia annua extracts and related products by high performance liquid chromatography-tandem mass spectrometry coupled to sample treatment miniaturisation
Protti, M., Mandrioli, R., Mandrone, M., Cappadone, C., Farruggia, G., Chiocchio, I., Malucelli, E., Isani, G., Poli, F., & Mercolini, L. (2019) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2019.05.044 · Cited by 13 · see citing works
Mutagenic effects of heavy-ion beam irradiation on in vitro nodal segments of Artemisia annua L.
Inthima, P., Otani, M., Hirano, T., Hayashi, Y., Abe, T., Nakano, M., & Supaibulwatana, K. (2014) · Plant Cell Tissue and Organ Culture (PCTOC) · doi:10.1007/s11240-014-0519-z · Cited by 13 · see citing works
“However, artemisinin yield in A. annua is relatively low and varies within the range of 0.1–1.4 % of dry weight (Delabays et al. 2001; Kumar P. Inthima K. Supaibulwatana (&) Department of Biotechnology, Faculty of Science, Mahidol University, 272 Rama VI Road, Ratchathewi District, Bangkok 10400,…”
Influential
Artemisia annua (Sweet Annie), Other Artemisia Species, Artemisinin, Artemisinin Derivatives, and Malaria
Yarnell, E. L. (2014) · Journal of Restorative Medicine · doi:10.14200/jrm.2014.3.0105 · Cited by 13 · see citing works
Studies on the expression of linalool synthase using a promoter-β-glucuronidase fusion in transgenic Artemisia annua
Wang, H., Kanagarajan, S., Han, J., Hao, M.-S., Yang, Y., Lundgren, A., & Brodelius, P. E. (2013) · Journal of Plant Physiology · doi:10.1016/j.jplph.2013.09.019 · Cited by 11 · see citing works
“Recently, two HAPs have been identified that produced up to 1.4% (Delabays et al., 2001) and 2% artemisinin (Cockram et al., 2012), respectively.”
BackgroundInfluential
Biosynthesis of artemisinin – revisited
Srivastava, N., & Akhila, A. (2011) · Journal of Plant Interactions · doi:10.1080/17429145.2011.570869 · Cited by 11 · see citing works
“Researchers are putting maximum effort for the last 25 years to obtain large amounts of artemisinin through synthesis or by enhancing the yields in the plant through biotechnological methods (Delabays et al. 2001; Sy and Brown 2002; Ferreira et al. 2005; Ro et al. 2006; Putalun et al. 2007).”
Background
In Vitro Adventitious Regeneration of Artemisia annua L. Influencing Artemisinin Metabolism
Blando, F., Rizzello, F., Durante, M., Paolis, A. D., Caretto, S., & Mita, G. (2021) · Horticulturae · doi:10.3390/horticulturae7110438 · Cited by 11 · see citing works
Breeding strategy for genetic improvement up to four generations in relation to artemisinin with canopy and other secondary metabolites in Artemisia annua L
Paul, S., Khanuja, S. P. S., & Gupta, M. M. (2014) · Industrial Crops and Products · doi:10.1016/j.indcrop.2014.02.008 · Cited by 10 · see citing works

Artemisinin evaluation in RomanianArtemisia annuawild plants using a new HPLC/MS method
Ivănescu, B., Vlase, L., Corciovă, A., & Lazar, M. I. (2011) · Natural Product Research · doi:10.1080/14786410903169847 · Cited by 19 · see citing works
Trichomes + roots + ROS = artemisinin: regulating artemisinin biosynthesis in Artemisia annua L.
Nguyen, K. T., Arsenault, P. R., & Weathers, P. J. (2011) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/s11627-011-9343-x · Cited by 66 · see citing works
Abscisic acid (ABA) treatment increases artemisinin content in Artemisia annua by enhancing the expression of genes in artemisinin biosynthetic pathway
Jing, F., Zhang, L., Li, M., Tang, Y., Wang, Y., Wang, Y., Wang, Q., Pan, Q., Wang, G., & Tang, K. (2009) · Biologia · doi:10.2478/s11756-009-0040-8 · Cited by 123 · see citing works
Metabolomics-Based Studies on Artemisinin Biosynthesis
Wang, H., Wang, H., Ma, C., Liu, B., Xu, G., & Ye, H. (2014) · Springer eBooks · doi:10.1007/978-94-017-9291-2_11 · Cited by 4 · see citing works
Assessment of Artemisinin Contents in Selected Artemisia Species from Tajikistan (Central Asia)
Numonov, S. R., Sharopov, F. S., Salimov, A., Sukhrobov, P., Atolikshoeva, S., Sharoffidin, R. S., Habasi, M., & Aisa, H. A. (2019) · Medicines · doi:10.3390/medicines6010023 · Cited by 71 · see citing works

Authors: Delabays, N., Simonnet, X., & Gaudin, M.
Venue: Current Medicinal Chemistry
Publisher: Bentham Science Publishers Ltd.
Published: 2001-12-01
Volume: 8
Issue: 15
Pages: 1795-1801
ISSN: 0929-8673 (ISSN-L)
DOI: 10.2174/0929867013371635
OpenAlex: W2134009021
Cited by: 178
References: 0
Citations by year: 2026: 6 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 9 · 2018: 14 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 17 · 2012: 10
FWCI: 1.36
Type: journal article
Language: en
Open access: closed
Locations: Current Medicinal Chemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Agricultural and Biological Sciences › Plant Science › Genetics and Plant Breeding
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Sesquiterpenes and Asteraceae Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
Keywords: artemisinin, Artemisia annua, artemisinin content, polygenic inheritance, narrow-sense heritability, additive genetic variance, dominance variance, mass selection, plant breeding, high-yielding varieties, genetic variation, hybrid lines
MeSH terms: Antimalarials, Cloning, Molecular, Crosses, Genetic, Sesquiterpenes, Artemisia, Artemisinins

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The Genetics of Artemisinin Content in Artemisia annua L. and the Breeding of High Yielding Cultivars

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