Present address: Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China.
The production of artemisinin precursors in tobacco
Article first published online: 18 AUG 2010
© 2010 NRC Canada. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd
Plant Biotechnology Journal
Volume 9, Issue 4, pages 445–454, May 2011
How to Cite
Zhang, Y., Nowak, G., Reed, D. W. and Covello, P. S. (2011), The production of artemisinin precursors in tobacco. Plant Biotechnology Journal, 9: 445–454. doi: 10.1111/j.1467-7652.2010.00556.x
- Issue published online: 17 APR 2011
- Article first published online: 18 AUG 2010
- Received 19 April 2010; accepted 13 July 2010.
- genetic engineering;
Artemisinin, in the form of artemisinin-based combination therapies (ACTs), is currently the most important compound in the treatment of malaria. The current commercial source of artemisinin is Artemisia annua, but this represents a relatively expensive source for supplying the developing world. In this study, the possibility of producing artemisinin in genetically modified plants is investigated, using tobacco as a model. Heterologous expression of A. annua amorphadiene synthase and CYP71AV1 in tobacco led to the accumulation of amorphadiene and artemisinic alcohol, but not artemisinic acid. Additional expression of artemisinic aldehyde Δ11(13) double-bond reductase (DBR2) with or without aldehyde dehydrogenase 1 (ALDH1) led to the additional accumulation dihydroartemisinic alcohol. The above-mentioned results and in vivo metabolic experiments suggest that amorphane sesquiterpenoid aldehydes are formed, but conditions in the transgenic tobacco cells favour reduction to alcohols rather than oxidation to acids. The biochemical and biotechnological significance of these results are discussed.