title: Artemisinin-based antimalarial research: application of biotechnology to the production of artemisinin, its mode of action, and the mechanism of resistance of Plasmodium parasites.
abstract: Malaria is a worldwide disease caused by Plasmodium parasites. A sesquiterpene endoperoxide artemisinin isolated from Artemisia annua was discovered and has been accepted for its use in artemisinin-based combinatorial therapies, as the most effective current antimalarial treatment. However, the quantity of this compound produced from the A. annua plant is very low, and the availability of artemisinin is insufficient to treat all infected patients. In addition, the emergence of artemisinin-resistant Plasmodium has been reported recently. Several techniques have been applied to enhance artemisinin availability, and studies related to its mode of action and the mechanism of resistance of malaria-causing parasites are ongoing. In this review, we summarize the application of modern technologies to improve the production of artemisinin, including our ongoing research on artemisinin biosynthetic genes in other Artemisia species. The current understanding of the mode of action of artemisinin as well as the mechanism of resistance against this compound in Plasmodium parasites is also presented. Finally, the current situation of malaria infection and the future direction of antimalarial drug development are discussed.
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Paskorn
authors.initials: P
authors.lastname: Muangphrom
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Seki
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.|Continuing Professional Development Center, Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Ery Odette
authors.initials: EO
authors.lastname: Fukushima
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. muranaka@bio.eng.osaka-u.ac.jp.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Muranaka
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry*; D001709:Biotechnology; D006801:Humans; D060847:Metabolic Engineering / Q000379:methods*; D010271:Parasites / Q000187:drug effects*; D010961:Plasmodium / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin
keywords: Artemisia annua; Artemisinin; Malaria; Metabolic engineering; Mode of action; Resistant parasites