Chapter 7 The Non-mevalonate DOXP/MEP (Deoxyxylulose 5-Phosphate/Methylerythritol 4-Phosphate) Pathway of Chloroplast Isoprenoid and Pigment Biosynthesis

The plastidic pathway for isopentenyl diphosphate (IPP) and isoprenoid biosynthesis, the DOXP/MEP pathway, possesses an essential function in the biosynthesis of thylakoidal prenylllipids chlorophylls (phytyl side-chain), carotenoids, plastoquinone-9, phylloquinone K1 and α-tocopherol, as well as for monoterpenes and diterpenes. Here we review its detection, its enzymes, intermediates, genes, cofactor requirements and inhibitors. This plastidic isoprenoid pathway is also contrasted against the acetate/mevalonate(MVA) pathway of isoprenoid biosynthesis operating in the cytosol for the biosynthesis of sterols, sesquiterpenes and polyterpenes. The DOXP/MEP pathway can specifically be inhibited by fosmidomycin and the acetate/MVA pathway by statins (e.g. mevinolin). By applying specifically marked substrates (2H-deoxyxylulose, 14C-DOXP, 3H-MVA or 14C-MVA) and specific inhibitors a cross-talk between both IPP yielding cell pathways was detected that operates preferentially in the chloroplast-to-cytosol direction. The DOXP/MEP pathway is also involved in the biosynthesis of the volatile hemiterpenes isoprene and methylbutenol. The distribution of the DOXP/MEP pathway in photosynthetic organisms (bacteria, algae, higher plants) and its putative origin in anoxigenic photosynthetic bacteria is reviewed. The DOXP/MEP pathway does not occur in Archaea, fungi or animals. The use of etiolated seedlings with their light-induced pigment accumulation as a test system for inhibitors of the DOXP/MEP pathway in the search of active ingredients against pathogenic bacteria and the malaria parasite Plasmodium is discussed.