Isoprenoid biosynthesis via 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway

Higher plants, several algae, bacteria, some strains of Streptomyces and po ssibly malaria parasite Plasmodium falciparum contain the novel, plastidic DOXP/MEP pathway for isoprenoid biosynthesis. This pathway, alternative wit h respect to the classical mevalonate pathway, starts with condensation of pyruvate and glyceraldehyde-3-phosphate which yields 1-deoxy-D-xylulose 5-p hosphate (DOXP); the latter product can be converted to isopentenyl diphosp hate (IPP) and eventually to isoprenoids or thiamine and pyridoxal. Subsequ ent reactions of this pathway involve transformation of DOXP to 2-C-methyl- D-erythritol 4-phosphate (MEP) which after condensation with CTP forms 4-di phosphocytidyl-2-C-methyl-D-erythritol (CDP-ME). Then CDP-ME is phosphoryla ted to 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) an d to 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (ME-2,4cPP) which is the last known intermediate of the DOXP/MEP pathway. Formation of IPP and dimet hylallyl diphosphate (DMAPP) from ME-2,4cPP still requires clarification. This novel pathway appears to be involved in biosynthesis of carotenoids, p hytol (side chain of chlorophylls), isoprene, mono-, di-, tetraterpenes and plastoquinone whereas the mevalonate pathway is responsible for formation of sterols, sesquiterpenes and triterpenes. Several isoprenoids were found to be of mixed origin suggesting that some exchange and/or cooperation exis ts between these two pathways of different biosynthetic origin. Contradicto ry results described below could indicate that these two pathways are opera ting under different physiological conditions of the cell and are dependent on the developmental state of plastids.