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The Molecular Mechanism of Action of Artemisinin—The Debate Continues
Molecules 2010, 15(4), 2302-2318; doi:10.3390/molecules15042302

Effect of Sugars on Artemisinin Production in Artemisia annua L.: Transcription and Metabolite Measurements

1, 2
1 Department of Biology and Biotechnology, Worcester Polytechnic Institute, WPI, 100 Institute Rd. Worcester MA 01609, USA 2 Arkansas Bioscience Institute, Arkansas State University, Jonesboro AR, 72401 USA 3 Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester MA, 01609, USA
* Author to whom correspondence should be addressed.
Received: 16 December 2009 / Revised: 20 March 2010 / Accepted: 23 March 2010 / Published: 30 March 2010
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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.
Keywords: terpene; sugar signal; secondary metabolism terpene; sugar signal; secondary metabolism
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Arsenault, P.R.; Vail, D.R.; Wobbe, K.K.; Weathers, P.J. Effect of Sugars on Artemisinin Production in Artemisia annua L.: Transcription and Metabolite Measurements. Molecules 2010, 15, 2302-2318.

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