HMG-CoA reductase limits artemisinin biosynthesis and accumulation in <Emphasis Type="Italic">Artemisia annua</Emphasis> L. plants |
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Authors: | Mauji Ram M A Khan Prabhakar Jha Salim Khan Usha Kiran M M Ahmad Saleem Javed M Z Abdin |
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Institution: | (1) Department of Biotechnology, Faculty of Science, Centre for Transgenic Plant Development, Jamia Hamdard, New Delhi, 110062, India;(2) Department of Botany, Faculty of Science, Jamia Hamdard, New Delhi, 110062, India;(3) Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia;(4) Department of Biochemistry, Faculty of Science, Jamia Hamdard, New Delhi, 110062, India; |
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Abstract: | 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 pre-flowering 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. |
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