Open AccessThe production of artemisinin precursors in tobacco
Author(s) -
Zhang Yansheng,
Nowak Goska,
Reed Darwin W.,
Covello Patrick S.
Publication year - 2011
Publication title -
plant biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.525
H-Index - 115
eISSN - 1467-7652
pISSN - 1467-7644
DOI - 10.1111/j.1467-7652.2010.00556.x
Subject(s) - artemisinin , artemisia annua , biology , biochemistry , aldehyde , nicotiana tabacum , transgene , aldehyde dehydrogenase , alcohol dehydrogenase , alcohol , enzyme , gene , plasmodium falciparum , malaria , catalysis , immunology
Summary 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.