Abstract
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.
Highlights
Artemisinin combination therapy (ACT) is the most effective means of treating malaria [1].Artemisinin (AN; Figure 1) is a sesquiterpene lactone that is produced by the plant Artemisia annua L.The plant has been part of traditional Chinese medicine for >2,000 years and used for a variety of ailments [2]
To determine if sugars were affecting the transcription of genes in the artemisinic biosynthetic pathways, we used Real-Time PCR to measure the relative transcript levels of the following genes: hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) deoxyxylulose-5-phosphate synthase (DXS), deoxyxylulouse 5phosphate reductoisomerase (DXR), farnesyl disphosphate (FPS), ADS, and CYP
Similar to methods used in sugar signaling studies in Arabidopsis, transcript levels were measured in seedlings grown in all three sugars with equimolar amounts of carbon
Summary
Artemisinin combination therapy (ACT) is the most effective means of treating malaria [1].Artemisinin (AN; Figure 1) is a sesquiterpene lactone that is produced by the plant Artemisia annua L.The plant has been part of traditional Chinese medicine for >2,000 years and used for a variety of ailments [2]. Artemisinin (AN; Figure 1) is a sesquiterpene lactone that is produced by the plant Artemisia annua L. AN may be an effective treatment for other health problems including those caused by cytomegalovirus, hepatitis B [3], schistosomiasis [4], and a variety of neoplasms [5]. Various attempts at increasing production have yielded some positive results but because the control of AN biosynthesis in planta is largely not understood, regulation of this terpenoid still requires considerable investigation. To our knowledge this is the first report showing kinetic changes in transcription of the genes in the AN biosynthetic pathway in A. annua in response to sugars
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