Biosynthesis in Artemisia Annua

Mercke, P., Bengtsson, M., Bouwmeester, H.J. etal. (2000) Molecular cloning, expression, and characterization of amorpha-4,11 -diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Archives of Biochemistry and Biophysics, 381, 173-180. 

Bertea CM, Freije JR, van der Wonde H, Verstappen FW, Perk L, Marquez V, De Kraker JW, Posthumus MA, Jansen BJ, de Groot A, Franssen MC, Bouwmeester HJ. (2005) Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua. Planta Med 71 40 7. 

Bertea, C.M., Voster, A., Verstappen, R W., Maffei, M., Beekwilder, J. and Bouwmeester, H.J. (2006) Isoprenoid biosynthesis in Artemisia annua cloning and heterologous expression of a germacrene A synthase from a glandular trichome cDNA library. Arch. Biochem. Biophys., 448, 3-12. 

Figure 4 Pathway of artemisinin biosynthesis in Artemisia annua. ADS, amorphadiene synthase CPR, cytochrome P450 reductase.

Zhang B, Zou T, Yan Hua Lu YH, Wang JW (2010) Stimulation of artemisinin biosynthesis in Artemisia annua hairy roots by oligogalacturonides. AM J Biotechnol 9 3437-3442... 

Wang JW, Xia ZH, Tan RX (2002) Elicitation on artemisinin biosynthesis in Artemisia annua hairy roots by the oligosaccharide extract frtnn the endophytic Colletotrichum sp. B501. Acta Bot Sin 44 1233-1238... 

Teoh KH, Polichuk DR, Reed DW, Covello PS (2009) Molecular cloning of an aldehyde dehydrogenase implicated in artemisinin biosynthesis in Artemisia annua. Botany 87 635-642... 

Ryden AM, Ruyter-Spira C, Quax WJ, Osada H, Muranaka T, Kayser O, Bouwmeester H (2010) The molecular cloning of dihydroartemisinic aldehyde reductase and its implication in artemisinin biosynthesis in Artemisia annua. Planta Med 76 1178-1183... 

Akhila A, Thakur RS, Popli SP (1987) Biosynthesis of artemisinin in Artemisia annua. Phytochem 16 1927-1930... 

Zhang YY, Teoh KH et al (2008) The molecular cloning of artemisinic aldehyde 11(13) reductase and its role in glandular trichome-dependent biosynthesis of artemisinin in Artemisia annua. J Biol Chem 283 21501-21508... 

Proteomics and metabolomics are thus key technologies in non-model plants for linking genes involved in the respective pathways with biosynthesis and accumulation of the natural compoimd. Huge efforts are presently invested in the elucidation of the biosynthetic pathways of anticancer (e.g. vinblastin in Catharanthus roseus or taxoids in Taxus baccata), antimalar-ial (artemisinin in Artemisia annua) drugs, or painkillers (e.g. morphine in the opium poppy) on different continents, supported by national and international programs. 

Chang YJ, Song SH, Park SH, Kim SU. (2000) Amorpha-4,11-diene synthase of Artemisia annua cDNA Isolation and bacterial expression of a terpene synthase involved in artemisinin biosynthesis. Arch Biochem Biophys 3S3 178-184. 

Schramek N, Wang HH, Romisch-Margl W, Keil B, Radykewicz T, Winzenhorlein B, Beerhues L, Bacher A, Rohdich F, Gershenzon J, Liu BY, Eisenreich W. (2010) Artemisinin biosynthesis in growing plants of Artemisia annua. A (C02)-C-13 study. Phytochemistry 71 179-187. 

Teoh KH, Polichuk DR, Reed DW, Nowak G Covello PS. (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 Lett 580 1411-1416. 

Brown, G. D. Cadinanes from Artemisia annua that may be intermediates in the biosynthesis of artemisinin. Phytochemistry, 1994, 36(3) 637-641. 

Artemisinin is used here as an example of a plant sesquiterpenoid with both traditional value as well as with medicinal and social value in the twenty-first century. Research on artemisinin has also established new benchmarks for biochemical engineering and functional genomics of plant terpenoids. Artemisinin is a functionalized sesquiterpene with a unique peroxide linkage from the sweet wormwood Artemisia annua). Chinese herbalists have used it since ancient times, and it is now used for its unique efficacy to treat multidrug-resistant strains of the malaria parasite Plasmodium falciparum. Its medicinal importance has prompted studies into its biosynthesis and its biochemical engineering so that cost-effective methods for producing it in large scale and in consistent quality may be realized. 

In contrast, in transgenic Artemisia annua plants overexpression of FPPS has been established. These plants were able to accumulate 34.4% more artemisinin, a novel antimalarial drug, than wild-type plants demonstrating the regulatory role of FPPS in the artemisin biosynthesis [333]. 

Aquil S, Husaini AM, Abdin MZ, Rather GM (2009) Overexpression of the HMG-CoA reductase gene leads to enhanced artemisinin biosynthesis in transgenic Artemisia annua plants. Planta Med 75 1-6... 

Chen J-L, Fang H-M, Ji Y-P et al (2011) Artemisinin biosynthesis enhanccanent in transgenic Artemisia annua plants by down-regulatisynthase gene. Planta Med 77 1759-1765... 

Guo C, Liu CZ, Ye HC, Li GF (2004) Effect of temperature on growth and artemisinin biosynthesis in hairy root cultures of Artemisia annua. Acta Bot Boreal-Occident Sin 24 1828-1831... 

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