Effect of Sugars on Artemisinin Production in Artemisia annua L.: Transcription and Metabolite Measurements
Open accessAbstract
The biosynthesis of the valuable sesquiterpene anti-malarial, artemisinin, is known to respond to exogenous sugar concentrations. Here young Artemisia annua L. seedlings (strain YU) were used to measure the transcripts of six key genes in artemisinin biosynthesis in response to growth on sucrose, glucose, or fructose. The measured genes are: from the cytosolic arm of terpene biosynthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), farnesyl disphosphate (FPS); from the plastid arm of terpene biosynthesis, 1-deoxyxylulose-5-phosphate synthase (DXS), 1-deoxyxylulouse 5-phosphate reductoisomerase (DXR); from the dedicated artemisinin pathway amorpha-4,11-diene synthase (ADS), and the P450, CYP71AV1 (CYP). Changes in intracellular concentrations of artemisinin (AN) and its precursors, dihydroartemisinic acid (DHAA), artemisinic acid (AA), and arteannuin B (AB) were also measured in response to these three sugars. FPS, DXS, DXR, ADS and CYP transcript levels increased after growth in glucose, but not fructose. However, the kinetics of these transcripts over 14 days was very different. AN levels were significantly increased in glucose-fed seedlings, while levels in fructose-fed seedlings were inhibited; in both conditions this response was only observed for 2 days after which AN was undetectable until day 14. In contrast to AN, on day 1 AB levels doubled in seedlings grown in fructose compared to those grown in glucose. Results showed that transcript level was often negatively correlated with the observed metabolite concentrations. When seedlings were gown in increasing levels of AN, some evidence of a feedback mechanism emerged, but mainly in the inhibition of AA production. Together these results show the complex interplay of exogenous sugars on the biosynthesis of artemisinin in young A. annua seedlings.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Feedback inhibition of artemisinin biosynthesis can occur; plants sprayed with artemisinic acid had reduced ADS transcripts.
“Feedback inhibition of artemisinin biosynthesis can also occur. Plants sprayed with artemisinic acid had reduced ADS transcripts of ADS A. annua (Arsenault et al. 2010).”
From Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches (2021) · cites this paper as Arsenault et al. 2010
The Results and Discussion section (‘Correlation between transcript and metabolite levels’; page unavailable) describes a possible negative correlation between ADS transcripts and artemisinic metabolites, suggesting a feedback mechanism. It does not report plants sprayed with artemisinic acid or a resulting reduction in ADS transcripts; its exogenous-treatment experiment instead added artemisinin to seedling culture medium and measured artemisinic acid levels. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Reactive oxygen species: Metabolism, oxidative stress, and signal transduction
Apel, K., & Hirt, H. (2004) · Annual Review of Plant Biology · doi:10.1146/annurev.arplant.55.031903.141701 · Cited by 11,723 · see citing works
Nutrient requirements of suspension cultures of soybean root cells
Gamborg, O. L., Miller, R. A., & Ojima, K. (1968) · Experimental Cell Research · doi:10.1016/0014-4827(68)90403-5 · Cited by 9,455 · see citing works
Reactive oxygen gene network of plants
Mittler, R., Vanderauwera, S., Gollery, M., & Breusegem, F. V. (2004) · Trends in Plant Science · doi:10.1016/j.tplants.2004.08.009 · Cited by 5,599 · see citing works
Asada, K. (1999) · Annual Review of Plant Physiology and Plant Molecular Biology · doi:10.1146/annurev.arplant.50.1.601 · Cited by 4,038 · see citing works
SUGAR SENSING AND SIGNALING IN PLANTS: Conserved and Novel Mechanisms
Rolland, F., Baena-Gonzalez, E., & Sheen, J. (2006) · Annual Review of Plant Biology · doi:10.1146/annurev.arplant.57.032905.105441 · Cited by 2,328 · see citing works
Statistical analysis of real-time PCR data
Yuan, J. S., Reed, A., Chen, F., & Stewart, C. N. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-85 · Cited by 2,192 · see citing works
Couée, I., Sulmon, C., Gouesbet, G., & Amrani, A. E. (2006) · Journal of Experimental Botany · doi:10.1093/jxb/erj027 · Cited by 1,121 · see citing works
Sucrose-Specific Induction of the Anthocyanin Biosynthetic Pathway in Arabidopsis
Solfanelli, C., Poggi, A., Loreti, E., Alpi, A., & Pierdomenico Perata, A. (2005) · PLANT PHYSIOLOGY · doi:10.1104/pp.105.072579 · Cited by 879 · see citing works
Rapid Induction of Distinct Stress Responses after the Release of Singlet Oxygen in Arabidopsis[W]
den Camp, R. O., Przybyla, D., Ochsenbein, C., Laloi, C., Kim, C., Danon, A., Wagner, D., Hideg, É., Göbel, C., Feußner, I., et al. (2003) · The Plant Cell · doi:10.1105/tpc.014662 · Cited by 748 · see citing works
Control of plant development and gene expression by sugar signaling
Gibson, S. I. (2004) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2004.11.003 · Cited by 697 · see citing works
Laule, O., Fürholz, A., Chang, H., Zhu, T., Wang, X., Heifetz, P. B., Gruissem, W., & Lange, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1031755100 · Cited by 692 · see citing works
Bhattarai, A., Ali, A. S., Kachur, S. P., Mårtensson, A., Abbas, A. K., Khatib, R., Al-mafazy, A.-W., Ramsan, M., Rotllant, G., Gerstenmaier, J. F., et al. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040309 · Cited by 647 · see citing works
The Genetic Basis of Singlet OxygenInduced Stress Responses of Arabidopsis thaliana
Wagner, D., Przybyla, D., den Camp, R. O., Kim, C., Landgraf, F., Lee, K. P., Würsch, M., Laloi, C., Nater, M., Hideg, É., et al. (2004) · Science · doi:10.1126/science.1103178 · Cited by 630 · see citing works
Differential regulation of EIN3 stability by glucose and ethylene signalling in plants
Yanagisawa, S., Yoo, S.-D., & Sheen, J. (2003) · Nature · doi:10.1038/nature01984 · Cited by 529 · see citing works
Zhou, L., Jang, J.-C., Jones, T. L., & Sheen, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.10294 · Cited by 483 · see citing works
Hemmerlin, A., Hoeffler, J., Meyer, O., Tritsch, D., Kagan, I. A., Grosdemange‐Billiard, C., Rohmer, M., & Bach, T. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302526200 · Cited by 436 · see citing works
Kolbe, A., Tiessen, A., Schluepmann, H., Paul, M. J., Ulrich, S., & Geigenberger, P. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503410102 · Cited by 411 · see citing works
Teoh, K. H., Polichuk, D. R., Reed, D. W., Nowak, G., & Covello, P. S. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.01.065 · Cited by 409 · see citing works
Redirection of cytosolic or plastidic isoprenoid precursors elevates terpene production in plants
Wu, S., Schalk, M., Clark, A., et al. (2006) · Nature Biotechnology · doi:10.1038/nbt1251 · Cited by 409 · see citing works
Číkoš, Š., Špirková, A., & Koppel, J. (2007) · BMC Molecular Biology · doi:10.1186/1471-2199-8-113 · Cited by 390 · see citing works
Zhang, Y., Teoh, K. H., Reed, D. W., Maes, L., Goossens, A., Olson, D. J. H., Ross, A. R. S., & Covello, P. S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803090200 · Cited by 312 · see citing works
Carbon Catabolite Repression Regulates Glyoxylate Cycle Gene Expression in Cucumber.
Graham, I. A., Denby, K., & Leaver, C. J. (1994) · The Plant Cell · doi:10.1105/tpc.6.5.761 · Cited by 283 · see citing works
Wallaart, T. E., Pras*, N., Beekman, A., & Quax, W. J. (2000) · Planta Medica · doi:10.1055/s-2000-11115 · Cited by 281 · cited 1× · see citing works
“Therefore an alternative explanation for increased biosynthesis of this particular secondary metabolite in response to glucose may be that AN and AB are formed as DHAA and AA, respectively, and act as sinks for reactive oxygen species (ROS), specifically singlet oxygen [33].”
Efferth, T. (2007) · Planta Medica · doi:10.1055/s-2007-967138 · Cited by 269 · see citing works
Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis
Bouwmeester, H. J., Wallaart, T. E., Janssen, M. H. A., van Loo, B., Jansen, B. J. M., Posthumus, M. A., Schmidt, C. O., De Kraker, J.-W., König, W. A., & Franssen, M. C. R. (1999) · Phytochemistry · doi:10.1016/s0031-9422(99)00206-x · Cited by 266 · see citing works
Artemisinin, a Novel Antimalarial Drug: Biochemical and Molecular Approaches for Enhanced Production
Abdin, M. Z., Israr, M., Rehman, R. U., & Jain, S. K. (2003) · Planta Medica · doi:10.1055/s-2003-38871 · Cited by 252 · see citing works
Wallaart, T. E., Bouwmeester, H. J., Hille, J., Poppinga, L., & Maijers, N. C. A. (2001) · Planta · doi:10.1007/s004250000428 · Cited by 242 · see citing works
Romero, M. R., Efferth, T., Serrano, M. A., Castaño, B., Macı́as, R. I. R., Briz, Ó., & Marı́n, J. J. G. (2005) · Antiviral Research · doi:10.1016/j.antiviral.2005.07.005 · Cited by 233 · see citing works
Chen, D.-H., Ye, H.-C., & Li, G.-F. (2000) · Plant Science · doi:10.1016/s0168-9452(00)00217-x · Cited by 225 · see citing works
Sugar sensing and Ca2+–calmodulin requirement in Vitis vinifera cells producing anthocyanins
Vitrac, X., Larronde, F., Krisa, S., et al. (2000) · Phytochemistry · doi:10.1016/s0031-9422(99)00620-2 · Cited by 205 · see citing works
Roldán, M., Gómez‐Mena, C., Ruiz‐García, L., et al. (1999) · The Plant Journal · doi:10.1046/j.1365-313x.1999.00632.x · Cited by 200 · see citing works
The history of qing hao in the Chinese materia medica
Hsü, E. (2006) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/j.trstmh.2005.09.020 · Cited by 199 · see citing works
Chadwick, A. E., Maggs, J. L., Sun, X.-M., Cohen, G. M., Chadwick, J., O’Neill, P. M., & Park, B. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610375200 · Cited by 192 · see citing works
Artemisinin, a Constituent of Annual Wormwood (Artemisia annua), is a Selective Phytotoxin
Duke, S. O., Vaughn, K. C., Croom, E. M., & ElSohly, H. N. (1987) · Weed Science · doi:10.1017/s0043174500060458 · Cited by 186 · see citing works
In vivo transformations of dihydroartemisinic acid in Artemisia annua plants
Brown, G. D., & Sy, L.-K. (2004) · Tetrahedron · doi:10.1016/j.tet.2003.11.070 · Cited by 183 · see citing works
Towler, M. J., & Weathers, P. J. (2007) · Plant Cell Reports · doi:10.1007/s00299-007-0420-x · Cited by 170 · see citing works
Self-citationExpression of the grape dihydroflavonol reductase gene and analysis of its promoter region
Gollop, R. (2002) · Journal of Experimental Botany · doi:10.1093/jexbot/53.373.1397 · Cited by 170 · see citing works
Functional genomics and the biosynthesis of artemisinin
Covello, P. S., Teoh, K. H., Polichuk, D. R., Reed, D. W., & Nowak, G. (2007) · Phytochemistry · doi:10.1016/j.phytochem.2007.02.016 · Cited by 152 · see citing works
Functional Genomics and the Biosynthesis of Artemisinin
Covello, P. S., Teoh, K. H., Polichuk, D. R., Reed, D. W., & Nowak, G. (2007) · ChemInform · doi:10.1002/chin.200742266 · Cited by 121 · see citing works
Oxidative Stress, Plant-Derived Antioxidants and Liver Fibrosis
Gebhardt, R. (2002) · Planta Medica · doi:10.1055/s-2002-26761 · Cited by 106 · see citing works
Carbon Catabolite Repression Regulates Glyoxylate Cycle Gene Expression in Cucumber
Graham, I. A., Denby, K., & Leaver, C. J. (1994) · The Plant Cell · doi:10.2307/3869878 · Cited by 104 · see citing works
Ma, C., Wang, H., Lu, X., Xu, G., & Liu, B. (2007) · Journal of Chromatography A · doi:10.1016/j.chroma.2007.09.023 · Cited by 103 · see citing works
Borrmann, S., Szlezák, N. A., Faucher, J., Matsiegui, P., Neubauer, R., Binder, R. K., Lell, B., & Kremsner, P. G. (2001) · The Journal of Infectious Diseases · doi:10.1086/324004 · Cited by 102 · see citing works
Wallaart, T. E., Pras, N., & Quax, W. J. (1999) · Journal of Natural Products · doi:10.1021/np9900122 · Cited by 101 · see citing works
Sucrose-mediated translational control
Hummel, M., Rahmani, F., SMEEKENS, S. C. M., & Hanson, J. (2009) · Annals of Botany · doi:10.1093/aob/mcp086 · Cited by 97 · see citing works
Sugars proportionately affect artemisinin production
Wang, Y., & Weathers, P. J. (2007) · Plant Cell Reports · doi:10.1007/s00299-006-0295-2 · Cited by 79 · see citing works
Self-citationCyclization mechanism of amorpha-4,11-diene synthase, a key enzyme in artemisinin biosynthesis
Kim, S.-H., Heo, K., Chang, Y.-J., Park, S.-H., Rhee, S.-K., & Kim, S.-U. (2006) · Journal of Natural Products · doi:10.1021/np050356u · Cited by 78 · see citing works
Mannan, A., Liu, C., Arsenault, P. R., Towler, M. J., Vail, D. R., Lorence, A., & Weathers, P. J. (2010) · Plant Cell Reports · doi:10.1007/s00299-009-0807-y · Cited by 75 · see citing works
Self-citationA comparative study of mist and bubble column reactors in the in vitro production of artemisinin
Kim, Y., Wyslouzil, B. E., & Weathers, P. J. (2001) · Plant Cell Reports · doi:10.1007/s002990100342 · Cited by 75 · see citing works
Self-citationKim, S.-H., Chang, Y., & Kim, S.-U. (2008) · Planta Medica · doi:10.1055/s-2008-1034276 · Cited by 51 · see citing works
Expression of the grape dihydroflavonol reductase gene and analysis of its promoter region 1
Gollop, R., Even, S., Colova-Tsolova, V., et al. (2002) · Journal of Experimental Botany · doi:10.1093/jxb/53.373.1397 · Cited by 48 · see citing works
Sehringer, B., Zahradnik, H. P., Deppert, W. R., Simon, M., Nöthling, C., & Schaefer, W. R. (2005) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-005-0067-9 · Cited by 22 · see citing works
POST-HARVEST DRYING TREATMENT EFFECTS ON AMTIMALARIAL CONSTITUENTS OF ARTEMIASIA ANNUA L.
Laughlin, J. C. (2002) · Acta Horticulturae · doi:10.17660/actahortic.2002.576.47 · Cited by 17 · see citing works
Scanning protein sequence databanks using a distributed processing workstation network
Barton, G. J. (1991) · Computer applications in the biosciences · doi:10.1093/bioinformatics/7.1.85 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Alam, P., & Abdin, M. Z. (2011) · Plant Cell Reports · doi:10.1007/s00299-011-1099-6 · Cited by 108 · see citing works
Wani, K. I., Choudhary, S., Zehra, A., Naeem, M., Weathers, P., & Aftab, T. (2021) · Planta · doi:10.1007/s00425-021-03676-3 · Cited by 74 · see citing works
Self-citationCold stress improves the production of artemisinin depending on the increase in endogenous jasmonate
Liu, W., Wang, H., Chen, Y., Zhu, S., Chen, M., Lan, X., Chen, G., & Liao, Z. (2017) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.1493 · Cited by 68 · see citing works
Molecular Farming in Artemisia annua, a Promising Approach to Improve Anti-malarial Drug Production
Pulice, G., Pelaz, S., & Matías-Hernández, L. (2016) · Frontiers in Plant Science · doi:10.3389/fpls.2016.00329 · Cited by 53 · see citing works
Zhou, L., Yang, G., Sun, H., Tang, J., Yang, J., Wang, Y., Garran, T. A., & Guo, L. (2017) · Frontiers of Medicine · doi:10.1007/s11684-016-0486-3 · Cited by 31 · see citing works
Nguyen, K. T., Towler, M. J., & Weathers, P. J. (2013) · Plant Cell Reports · doi:10.1007/s00299-012-1355-4 · Cited by 27 · see citing works
Self-citation
- Authors
- Arsenault, P. R., Vail, D. R., Wobbe, K. K., & Weathers, P. J.
- Affiliations
- Worcester Polytechnic Institute (US)
- Arkansas State University (US)
- Corresponding author
- Weathers, Pamela J.
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2010-03-30
- Volume
- 15
- Issue
- 4
- Pages
- 2302-2318
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC3939791
- OpenAlex
- W1969427904
- Cited by
- 54
- References
- 55
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 2 · 2016: 6 · 2015: 6 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital WPI (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Arkansas Biosciences Institute
- National Institutes of Health
- National Institute of General Medical Sciences (R15GM069562)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant tissue culture and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Sesquiterpenes and Asteraceae Studies
- Keywords
- artemisinin biosynthesis, Artemisia annua, sugar metabolism, glucose, fructose, sucrose, sesquiterpene biosynthesis, terpene synthase genes, CYP71AV1, dihydroartemisinic acid, artemisinic acid, arteannuin B, product inhibition, gene expression, metabolite concentrations, antimalarial compounds
- MeSH terms
- Antimalarials, Fructose, Glucose, Sucrose, Transcription, Genetic, Artemisia annua, Artemisinins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
