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Myiophagus characeus Kiran et Dayal, sp.nov.

100%

Kiran U. , Dayal R.

Acta Mycologica

1997

tom 32

nr 1

HMG-CoA reductase limits artemisinin biosynthesis and accumulation in Artemisia annua L. plants

51%

Ram M. , Khan M. A. , Jha P. , Khan S. , Kiran U. , Ahmad M. M. , Javed S. , Abdin M. Z.

Acta Physiologiae Plantarum

2010

tom 32

nr 5

In vivo modulation of HMG-CoA reductase (HMGR) activity and its impact on artemisinin biosynthesis as well as accumulation were studied through exogenous supply of labeled HMG-CoA (substrate), labeled MVA (the product), and mevinolin (the competitive inhibitor) using twigs of Artemisia annua L. plants collected at the preflowering stage. By increasing the concentration (2–16 µM) of HMG-CoA (3-¹⁴C), incorporation of labeled carbon into artemisinin was enhanced from 7.5 to 17.3 nmol (up to 130%). The incorporation of label (¹⁴C) into MVA and artemisinin was inhibited up to 87.5 and 82.9%, respectively, in the presence of 200 µM mevinolin in incubation medium containing 12 µM HMG-CoA (3-¹⁴C). Interestingly, by increasing the concentration of MVA (2-¹⁴C) from 2 to 18 µM, incorporation of label (¹⁴C) into artemisinin was enhanced from 10.5 to 35 nmol (up to 233%). When HMG-CoA (3-¹⁴C) concentration was increased from 12 to 28 µM in the presence of 150 µM mevinolin, the inhibitions in the incorporation of label (¹⁴C) into MVA and artemisinin were, however, reversed and the labels were found to approach their values in twigs fed with 12 µM HMG-CoA (3-¹⁴C) without mevinolin. In another experiment, 14.2% inhibition in artemisinin accumulation was observed in twigs in the presence of 175 µM fosmidomycin, the competitive inhibitor of 1-deoxy-D-xylulose 5-phosphate reductase (DXR). HMG-CoA reductase activity and artemisinin accumulation were also increased by 18.6 to 24.5% and 30.7 to 38.4%, respectively, after 12 h of treatment, when growth hormones IAA (100 ppm), GA₃ (100 ppm) and IAA + GA₃ (50 + 50 ppm) were sprayed on A. annua plants at the pre-flowering stage. The results obtained in this study, hence, demonstrate that the mevalonate pathway is the major contributor of carbon supply to artemisinin biosynthesis and HMGR limits artemisinin synthesis and its accumulation in A. annua plants.