Search

Artemisinin is a well-known antimalarial drug isolated from the Artemisia annua plant. The biosynthesis of this well-known molecule has been reinvestigated by using [1-13C]acetate, [2-13C]acetate, and [1,6-13C2]glucose. The 13C peak enrichment in artemisinin was observed in six and nine carbon atoms from [1-13C]acetate and [2-13C]acetate, respectively. The 13C NMR spectra of 13C-enriched artemisinin suggested that the mevalonic acid (MVA) pathway is the predominant route to biosynthesis of this sesquiterpene. On the other hand, the peak enrichment of five carbons of 13C-artemisinin including carbon atoms originating from methyls of dimethylallyl group of geranyl pyrophosphate (GPP) and farnesyl pyrophosphate (FPP) was observed from [1,6-13C2]glucose. This suggested that GPP which is supposed to be biosynthesized in plastids travels from plastids to cytosol through the plastidial wall and combines with isopentenyl pyrophosphate (IPP) to form the (E,E)-FPP which finally cyclizes and oxidizes to artemisinin. In this way the DXP pathway also contributes to the biosynthesis of this sesquiterpene. [ABSTRACT FROM PUBLISHER]

Isoprenoids are a large and structurally diverse family of compounds that play essential roles in plants as hormones, photosynthetic pigments, electron carriers, and membrane components as well as serving in communication and defense. Now it is unequivocally proved that two distinct and independent biosynthetic routes exist to isopentenyl diphosphate (IPP) and its allylic isomer dimethylallyl diphosphate (DMAPP), the two building blocks for isoprenoids in plants. The cytosolic pathway is triggered by Acetyl Coenzyme A where classical intermediate mevalonic acid is formed which, in turn, converts into IPP and DMAPP. These further combine to elongate into sesquiterpenes (C15) and triterpenes (C30); whereas the plastidial pathway provides precursors for the biosynthesis of isoprene (C5), monoterpenes (C10), diterpenes (C20), and tetraterpenes (C40). The pathway is initiated by the transketolase-type condensation of pyruvate (C-2 and C-3) and glyceraldehyde-3-phosphate to 1-deoxyxylulose-5-phosphate (DXP), followed by the isomerization and reduction of this intermediate to 2-C-methylerythritol-4-phosphate (MEP), formation of the cytidine 5'-diphosphate (CDP) derivative, phosphorylation at C2, and cyclization to 2-C-methylerythritol-2,4-cyclodiphosphate (CDP-Me2P as the last defined step). The genes encoding each enzyme of the plastid pathway up to formation of the cyclic diphosphate have been isolated from plants and from eubacteria where the pathway exists. Studies on the complete biosynthetic pathways using radio-labeled substrates will help in characterizing and identifying the enzymes involved in each and every step of cyclization, isomerization, chain elongation, hydrogen shifts, oxidation and hydroxylation during the formation of many isoprenoid compounds present in food and flavor substances and are highly useful to human beings. [ABSTRACT FROM AUTHOR]