Metabolic engineering of plants for artemisinin synthesis

Biotechnology and Genetic Engineering Reviews

Volumn 29, Issue 2, 2013, Pages 135-148

  Farhi, Moran ^a,b   Kozin, Magali ^a   Duchin, Shai ^a   Vainstein, Alexander ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Artemisia annua; Artemisinin; Malaria; Metabolic engineering

Indexed keywords

BIOCHEMISTRY; BIOSYNTHESIS; DISEASES; METABOLISM; PLANTS (BOTANY);

ARTEMISIA ANNUA; ARTEMISININ; DRUG-RESISTANT MALARIA; GENETIC RESOURCES; MALARIA; MOLECULAR BREEDING; NATIVE PLANTS; NATURAL COMPOUNDS; TERPENOIDS; TRANSGENESIS;

METABOLIC ENGINEERING;

ARTEMISININ; MEVALONIC ACID; SESQUITERPENE; ARTEMISININ DERIVATIVE;

ARTEMISIA ANNUA; ARTICLE; CELL METABOLISM; DRUG SYNTHESIS; GENE ACTIVATION; GENE REPRESSION; HOST; METABOLIC ENGINEERING; PRECURSOR; SYNTHETIC BIOLOGY; TRANSGENICS; CHEMISTRY; GENETICS; HUMAN; MALARIA; PATHOLOGY; PLANT; PROCEDURES; SYNTHESIS;

ARTEMISIA ANNUA;

ARTEMISIA ANNUA; ARTEMISININS; HUMANS; MALARIA; METABOLIC ENGINEERING; PLANTS; SYNTHETIC BIOLOGY;

EID: 84887461647     PISSN: 02648725     EISSN: None     Source Type: Journal    
DOI: 10.1080/02648725.2013.821283     Document Type: Article

References (62)

1. Abdin, M. Z., Israr, M., Rehman, R. U., & Jain, S. K. (2003). Artemisinin, a novel antimalarial drug: Biochemical and molecular approaches for enhanced production. Planta Medica, 69, 289-299.
2. Alam, P., & Abdin, M. Z. (2011). Over-expression of HMG-CoA reductase and amorpha-4, 11-diene synthase genes in Artemisia annua L. and its influence on artemisinin content. Plant Cell Reports, 30, 1919-1928.
3. Anthony, J. R., Anthony, L. C., Nowroozi, F., Know, G., Newman, J. D., & Keasling, J. D. (2009). Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene. Metabolic Engineering, 11, 13-19.
4. Aquil, S., Husaini, A. M., Abdin, M. Z., & Rather, G. M. (2009). Overexpression of the HMGCoA reductase gene leads to enhanced artemisinin biosynthesis in transgenic Artemisia annua plants. Planta Medica, 75, 1453-1458.
5. Arsenault, P. R., Vail, D., Wobbe, K. K., Erickson, K., & Wethers, P. J. (2010). Reproductive development modulates gene expression and metabolite levels with possible feedback inhibition of artemisinin in Artemisia annua. Plant Physiology, 154, 958-968.
6. Banerjee, S., Zehra, M., Gupta, M. M., & Kuma, S. (1997). Agrobacterium rhizogenes mediated transformation of Artemisia annua: Production of transgenic plants. Planta Medica, 63, 467-469.
7. Bouvier, F., Rahier, A., & Camara, B. (2005). Biogenesis, molecular regulation and function of plant isoprenoids. Progress in Lipid Research, 44, 357-429.
8. Brown, G. D. (2010). The biosynthesis of artemisinin (Qinghaosu) and the phytochemistry of Artemisia annua L. (Qinghao). Molecules, 15, 7603-7698.
9. Chappell, J., Wolf, F., Proulx, J., Cuellar, R., & Saunders, C. (1995). Is the reaction catalyzed by 3-hydroxy-3-methylglutaryl coenzyme A reductase a rate-limiting step for isoprenoid biosynthesis in plants? Plant Physiology, 109, 1337-1343.
10. Chen, J.-L., Fang, H.-M., Ji, Y.-P., Pu, G.-B., Guo, Y.-W., Huang, L.-L., ... Wang, H. (2011). Artemisinin biosynthesis enhancement in transgenic Artemisia annua plants by downregulation of the β-caryophyllene synthase gene. Planta Medica, 77, 1759-1765.
11. Chen, D. H., Ye, H. C., & Li, G. F. (2000). Expression of a chimeric farnesyl diphosphate synthase gene in Artemisia annua L. transgenic plants via Agrobacterium tumefaciens-mediated transformation. Plant Science, 155, 179-185.
12. Chico, R. M., Mayaud, P., Ariti, C., Mabey, D., Ronsmans, C., & Chandramohan, D. (2012). Prevalence of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: A systematic review. Journal of the American Medical Association, 307, 2079-2086.
13. Covello, P. S. (2008). Making artemisinin. Phytochemistry, 69, 2881-2885.
14. Covello, P. S., Teoh, K. H., Polichuk, D. R., Reed, D. W., & Nowak, G. (2007). Functional genomics and the biosynthesis of artemisinin. Phytochemistry, 68, 1864-1871.
15. Croteau, R., Davis, E., Ringer, K., & Wildung, M. (2005). (-)-Menthol biosynthesis and molecular genetics. Naturwissenschaften, 92, 562-577.
16. Dudareva, N., Andersson, S., Orlova, I., Gatto, N., Reichelt, M., Rhodes, D., ... Gershenzon, J. (2005). The nonmevalonate pathway supports both monoterpene and sesquiterpene formation in snapdragon flowers. Proceedings of the National Academy of Sciences of the United States of America, 102, 933-938.
17. Efferth, T. (2006). Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells. Current Drug Targets, 7, 407-421.
18. Farhi, M., Marhevka, E., Ben-Ari, J., Algamas-Dimantov, A., Liang, Z., Zeevi, V., ... Vainstein, A. (2011). Generation of the potent anti-malarial drug artemisinin in tobacco. Nature Biotechnology, 29, 1072-1074.
19. Farhi, M., Marhevka, E., Masci, T., Marcos, E., Eyal, Y., Ovadis, M., ... Vainstein, A. (2011). Harnessing yeast subcellular compartments for the production of plant terpenoids. Metabolic Engineering, 13, 474-481.
20. Firestone, G. L., & Sundar, S. N. (2009). Anticancer activities of artemisinin and its bioactive derivatives. Expert Reviews in Molecular Medicine, 11, e32.
21. Graham, I. A., Besser, K., Blumer, S., Branigan, C. A., Czechowski, T., Elias, L., ... Bowles, D. (2010). The genetic map of Artemisia annua L. identifies loci affecting yield of the antimalarial drug artemisinin. Science, 327, 328-331.
22. Kappers, I. F., Aharoni, A., & van Herpen, T. W. J. M. (2005). Genetic engineering of terpenoid metabolism attracts bodyguards to Arabidopsis. Science, 309, 2070-2072.
23. Keasling, J. D. (2010). Manufacturing molecules through metabolic engineering. Science, 330, 1355-1358.
24. Krichevsky, A., Zaltsman, A., King, L., & Citovsky, V. (2012). Expression of complete metabolic pathways in transgenic plants. Biotechnology and Genetic Engineering Reviews, 28, 1-13.
25. Kumar, S., Hahn, F. M., Baidoo, E., Kahlon, T. S., Wood, D. F., McMahan, C. M., ... Whalen, M. C. (2012). Remodeling the isoprenoid pathway in tobacco by expressing the cytoplasmic mevalonate pathway in chloroplasts. Metabolic Engineering, 14, 19-28.
26. Kupferschmidt, K. (2012). Can new chemistry make a malaria drug plentiful and cheap? Science, 336, 798-799.
27. Liu, B., Wang, H., Du, Z., Li, G., & Ye, H. (2011). Metabolic engineering of artemisinin biosynthesis in Artemisia annua L. Plant Cell Reports, 30, 689-694.
28. Lubertozzi, D., & Keasling, J. (2008). Expression of a synthetic Artemisia annua amorphadiene synthase in Aspergillus nidulans yields altered product distribution. Journal of Industrial Microbiology & Biotechnology, 35, 1191-1198.
29. Ma, D., Pu, G., Lei, C., Ma, L., Wang, H., Guo, Y., ... Liu, B. (2009). Isolation and characterization of Aa WRKY1, an Artemisia annua transcription factor that regulates the amorpha-4, 11-diene synthase gene, a key gene of artemisinin biosynthesis. Plant and Cell Physiology, 50, 2146-2161.
30. Ma, C., Wang, H., Lu, X., Wang, H., Xu, G., & Liu, B. (2009). Terpenoid metabolic profiling analysis of transgenic Artemisia annua L. by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. Metabolomics, 5, 497-506.
31. Marsh, K. (1998). Malaria disaster in Africa. Lancet, 352, 924-924.
32. Mazuz, M. L., Haynes, R., Shkap, V., Fish, L., Wollkomirsky, R., Leibovich, B., Molad, T., Savitsky, I., & Golenser, J. (2012). Neospora caninum: In vivo and In vitro treatment with artemisone. Veterinary Parasitology, 187, 99-104.
33. Moyal Ben Zvi, M., Negre-Zakharov, F., Masci, T., Ovadis, M., Shklarman, E., Ben-Meir, H., ... Vainstein, A. (2008). Interlinking showy traits: Co-engineering of scent and colour biosynthesis in flowers. Plant Biotechnology Journal, 6, 403-415.
34. Nayyar, G. M. L., Breman, J. G., Newton, P. N., & Herrington, J. (2012). Poor-quality antimalarial drugs in Southeast Asia and sub-Saharan Africa. The Lancet Infectious Diseases, 12, 488-496.
35. Olsson, M. E., Olofsson, L. M., Lindahl, A.-L., Lundgren, A., Brodelius, M., & Brodelius, P. E. (2009). Localization of enzymes of artemisinin biosynthesis to the apical cells of glandular secretory trichomes of Artemisia annua L. Phytochemistry, 70, 1123-1128.
36. Paniego, N. B., & Giulietti, A. M. (1996). Artemisinin production by Artemisia annua Ltransformed organ cultures. Enzyme and Microbial Technology, 18, 526-530.
37. Paradise, E. M., Kirby, J., Chan, R., & Keasling, J. D. (2008). Redirection of flux through the FPP branch-point in Saccharomyces cerevisiae by down-regulating squalene synthase. Biotechnology and Bioengineering, 100, 371-378.
38. Pu, G.-B., Ma, D.-M., Wang, H., Ye, H.-C., & Liu, B.-Y. (2013). Expression and localization of amorpha-4,11-diene synthase in Artemisia annua L. Plant Molecular Biology Reporter, 31, 32-37.
39. Pulido, P., Perello, C., & Rodriguez-Concepcion, M. (2012). New insights into plant isoprenoid metabolism. Molecular Plant, 5, 964-967.
40. Ro, D.-K., Paradise, E. M., Ouellet, M., Fisher, K. J., Newman, K. L., Ndungu, J. M., ... Keasling, J. D. (2006). Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature, 440, 940-943.
41. Roberts, S., & Kolewe, M. (2010). Plant natural products from cultured multipotent cells. Nature Biotechnology, 28, 1175-1176.
42. Rontein, D., Onillon, S., Herbette, G., Lesot, A., Werck-Reichhart, D., Sallaud, C., & Tissier, A. (2008). CYP725A4 from yew catalyzes complex structural rearrangement of taxa-4(5),11(12)-diene into the cyclic ether 5(12)-oxa-3(11)-cyclotaxane. Journal of Biological Chemistry, 283, 6067-6075.
43. 2 study. Phytochemistry, 71, 179-187.
44. Spitzer-Rimon, B., Farhi, M., Albo, B., Cna'ani, A., Moyal Ben-Zvi, M., Masci, T., ... Vainstein, A. (2012). EOBI, acting downstream of EOBII, regulates scent production by activating ODO1 and structural scent-related genes. The Plant Cell, 24, 5089-5105.
45. Teoh, K. H., Polichuk, D. R., Reed, D. W., & Covello, P. S. (2006). Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin. FEBS Letters, 580, 1411-1416.
46. Teoh, K. H., Polichuk, D. R., Reed, D. W., Nowak, G., & Covello, P. S. (2009). Molecular cloning of an aldehyde dehydrogenase implicated in artemisinin biosynthesis in Artemisia annua. Botany, 87, 635-642.
47. Towler, M., & Weathers, P. (2007). Evidence of artemisinin production from IPP stemming from both the mevalonate and the nonmevalonate pathways. Plant Cell Reports, 26, 2129-2136.
48. Urban, P., Mignotte, C., Kazmaier, M., Delorme, F., & Pompon, D. (1997). Cloning, yeast expression, and characterization of the coupling of two distantly related Arabidopsis thaliana NADPH-cytochrome P450 reductases with P450 CYP73A5. Journal of Biological Chemistry, 272, 19176-19186.
49. Van Herpen, T. W. J. M., Cankar, K., Nogueira, M., Bosch, D., Bouwmeester, H. J., & Beekwilder, J. (2010). Nicotiana benthamiana as a production platform for artemisinin precursors. PLoS ONE, 5, e14222.
50. Van Noorden, R. (2010). Demand for malaria drug soars. Nature, 466, 672-673.
51. Vergauwe, A., Cammaert, R., Vandenberghe, D., Genetello, C., Inze, D., Van Montagu, M., & Van-Den Eeckhout, E. (1996). Agrobacterium tumefaciens-mediated transformation of Artemisia annua L. and regeneration of transgenic plants. Plant Cell Reports, 15, 929-933.
52. Wallaart, T. E., Bouwmeester, H. J., Hille, J., Poppinga, L., & Maijers, N. C. A. (2001). Amorpha-4,11-diene synthase: Cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin. Planta, 212, 460-465.
53. Wang, H., Han, J., Kanagarajan., S., Lundgren, A., & Brodelius, P. E. (2013). Trichome-specific expression of the amorpha-4,11-diene 12-hydroxylase (cyp71av1) gene, encoding a key enzyme of artemisinin biosynthesis in Artemisia annua, as reported by a promoter-GUS fusion. Plant Molecular Biology, 81, 119-138.
54. Wang, H., Nagegowda, D. A., Rawat, R., Bouvier-Navé, P., Guo, D., Bach, T. J., & Chye, M.-L. (2012). Overexpression of Brassica juncea wild-type and mutant HMG-CoA synthase 1 in Arabidopsis up-regulates genes in sterol biosynthesis and enhances sterol production and stress tolerance. Plant Biotechnology Journal, 10, 31-42.
55. WHO. (2005). World Malaria Report. Geneva: World Health Organization.
56. Wilson, S. A., & Roberts, S. C. (2012). Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. Plant Biotechnology Journal, 10, 249-268.
57. Wu, S., Schalk, M., Clark, A., Miles, R. B., Coates, R., & Chappell, J. (2006). Redirection of cytosolic or plastidic isoprenoid precursors elevates terpene production in plants. Nature Biotechnology, 24, 1441-1447.
58. Yang, R.-Y., Feng, L.-L., Yang, X.-Q., Yin, L.-L., Xu, X.-L., & Zeng, Q.-P. (2008). Quantitative transcript profiling reveals down-regulation of a sterol pathway relevant gene and overexpression of artemisinin biogenetic genes in transgenic Artemisia annua plants. Planta Medica, 74, 1510-1516.
59. Yu, Z.-X., Li, J.-X., Yang, C.-Q., Hu, W.-L., Wang, L.-J., & Chen, X.-Y. (2012). The jasmonateresponsive AP2/ERF transcription factors AaERF1 and AaERF2 positively regulate artemisinin biosynthesis in Artemisia annua L. Molecular Plant, 5, 353-365.
60. Zhang, L., Jing, F., Li, F., Li, M., Wang, Y., Wang, G., ... Tang, K. (2009). Development of transgenic Artemisia annua (Chinese wormwood) plants with an enhanced content of artemisinin, an effective anti-malarial drug, by hairpin-RNA-mediated gene silencing. Biotechnology and Applied Biochemistry, 52, 199-207.
61. Zhang, Y., Nowak, G., Reed, D. W., & Covello, P. S. (2011). The production of artemisinin precursors in tobacco. Plant Biotechnology Journal, 9, 445-454.
62. Zhang, Y., Teoh, K. H., Reed, D. W., Maes, L., Goossens, A., Olson, D. J. H., ... Covello, P. S. (2008). The molecular cloning of artemisinic aldehyde Delta 11(13) reductase and its role in glandular trichome-dependent biosynthesis of artemisinin in Artemisia annua. Journal of Biological Chemistry, 283, 21501-21508.