青蒿素生物合成分子调控研究进展

Advances in Molecular Regulation of Artemisinin Biosynthesis

青蒿素是目前世界上最有效的疟疾治疗药物。通过对青蒿素的生物合成途径 ,青蒿素生物合成途径的关键酶 ,青蒿素生物合成的分子调控的介绍 ,综述了青蒿素生物合成分子调控的最新研究进展。

Artemisinin, a new and a very potent antimalarial drug, is produced by the Chinese medicinal herb %Artemisia annua% L. It is a sesquiterpene lactone with an endoperoxide bridge and is active against chloroquine resistant forms of %Plasmodium falciparum.% The relatively low yield (0 01%～0 6%) of artemisinin in %A. annua% is a serious limitation to the commercialization of the drug. Therefore, a through understanding of the biosynthetic pathway and the characterization of the involved enzymes are important for the biology production of artemisinin. This review is focused on the recent progress in the molecular regulation of artemisinin biosynthesis from the following aspects: the biosynthetic pathway of artemisinin, the key enzymes involved in artemisinin biosynthesis, and the molecular regulation of artemisinin biosynthesis. The biosynthetic pathway of artemisinin belongs to the isoprenoid metabolite pathway, the key enzymes involved in the biosynthesis of artemisinin include: 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), farnesyl diphosphate synthase (FDPS), and amorpha-4,11-diene synthase, of which amorpha-4,11-diene synthase catalyzes the cyclisation of the ubiquitous precursor farnesyl diphosphate to the highly specific olefinic sesquiterpene skeletons and has been postulated as the regulatory step in the biosynthesis of artemisinin. Recently the gene encoding of the amorpha-4,11-diene synthase has been cloned and the functional expressions have been studied by several research teams, therefore, the breakthroughs in production of artemisinin could hopefully be achieved by metabolic engineering of the plant, in particular, by over-expressing enzyme(s) catalyzing the rate limiting step(s) of artemisinin biosynthesis or by inhibiting the enzyme(s) of other pathway competing for its precursors. Besides, the effects of the heterogenesis isoprenoid pathway related genes on artemisinin biosynthesis of the transformed plants were also discussed.