title: Overexpression and Suppression ofArtemisia annua4-Hydroxy-3-Methylbut-2-enyl Diphosphate Reductase 1 Gene (AaHDR1) Differentially Regulate Artemisinin and Terpenoid Biosynthesis.
abstract: 4-Hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR) catalyzes the last step of the 2-C-methyl-D-erythritol 4- phosphate (MEP) pathway to synthesize isopentenyl pyrophosphate (IPP) and dimethylallyl diphosphate (DMAPP). To date, little is known regarding effects of an increase or a decrease of aHDRexpression on terpenoid and other metabolite profiles in plants. In our study, anArtemisia annua HDRcDNA (namelyAaHDR1) was cloned from leaves. Expression profiling showed that it was highly expressed in leaves, roots, stems, and flowers with different levels. Green florescence protein fusion and confocal microscope analyses showed that AaHDR1 was localized in chloroplasts. The overexpression ofAaHDR1increased contents of artemisinin, arteannuin B and other sesquiterpenes, and multiple monoterpenes. By contrast, the suppression ofAaHDR1by anti-sense led to opposite results. In addition, an untargeted metabolic profiling showed that the overexpression and suppression altered non-polar metabolite profiles. In conclusion, the overexpression and suppression of AaHDR1 protein level in plastids differentially affect artemisinin and other terpenoid biosynthesis, and alter non-polar metabolite profiles ofA. annua. Particularly, its overexpression leading to the increase of artemisinin production is informative to future metabolic engineering of this antimalarial medicine.
authors.affiliation: Department of Plant and Microbial biology, North Carolina State University, Raleigh, NC USA.
authors.forename: Dongming
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Plant and Microbial biology, North Carolina State University, Raleigh, NC USA.
authors.forename: Gui
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Plant and Microbial biology, North Carolina State University, Raleigh, NC USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Plant and Microbial biology, North Carolina State University, Raleigh, NC USA.
authors.forename: De-Yu
authors.initials: DY
authors.lastname: Xie
keywords: 4-Hydroxy-3-methylbut-2-enyl diphosphate reductase; Artemisia annua; arteannuin B; artemisinin; methylerythritol phosphate pathway; terpene