methylerythritol phosphate pathway

The methylerythritol phosphate pathway provides a route to isoprenoid biosynthesis in the plastids of plants, in protozoa, and in prokaryotes. Plants also employ the HMG-CoA-reductase pathway to manufacture isoprenoids - small image, 128 k image.

Isopentenyl diphosphate (IPP) is the fundamental unit in isoprenoid biosynthesis. E. coli utilizes a mevalonate-independent pathway for synthesis of IPP. In the initial step 1-deoxy-D-xylulose 5-phosphate (DXP) is formed by condensation of pyruvate and glyceraldehyde 3-phosphate. In the second step DXP is rearranged and reduced in a single reaction yielding 2-C-methyl-D-erythritol 4-phosphate (MEP). In the third reaction MEP is converted into 4-diphosphocytidyl-2-C-methylerythritol, which is subsequently phosphorylated at the 2 position hydroxy group yielding 4-diphosphocytidyl-2C-methylerythritol 2-phosphate. This product is then converted into 2-C-methyl-D-erythritol 2,4-cyclodiphosphate. [ Takahashi98 , Sprenger97 , Lois98 , Lange98 , Rohmer93 , Luttgen00 , Rohdich99 , Herz00 ] The final two steps are catalyzed by the IspG and IspH proteins, respectively [ Hecht01 , Rohdich02 ] . [source]

In the bacterium Bacillus subtilis, isoprene is not formed by the mevalonate pathway or from catabolism of leucine, but, as in plant systems, it is a product of the methylerythritol phosphate pathway of isoprenoid synthesis.

Two genes encoding the enzymes 1-deoxy-D-xylulose-5-phosphate synthase and 1-deoxy-D-xylulose-5-phosphate reductoisomerase have been recently identified, suggesting that isoprenoid biosynthesis in Plasmodium falciparum depends on the methylerythritol phosphate (MEP) pathway, and that fosmidomycin could inhibit the activity of 1-deoxy-D-xylulose-5-phosphate reductoisomerase. The metabolite 1-deoxy-D-xylulose-5-phosphate is not only an intermediate of the MEP pathway for the biosynthesis of isopentenyl diphosphate but is also involved in the biosynthesis of thiamin (vitamin B1) and pyridoxal (vitamin B6) in plants and many microorganisms. The MEP pathway is functionally active in all intraerythrocytic forms of P. falciparum, demonstrating de novo biosynthesis of pyridoxal in a protozoan. The absence of the MEP pathway and isoprenoid biosynthesis in the human host makes both pathways very attractive as potential new targets for antimalarial drug development.[a]

The MEP pathway is not present in humans and it is involved in the production of phosphate-containing antigens recognized by γ-δ T lymphocytes.

Biosynthetic Routes to the Building Blocks of Isoprenoids pdf : Mycorrhiza Literature Exchange : Plant Biol : Elucidation of the Methylerythritol Phosphate Pathway for Isoprenoid Biosynthesis in Bacteria and Plastids. A ... :

Synonyms: methylerythritol phosphate pathway, nonmevalonate isopentenyl diphosphate biosynthesis, methylerythritol phosphate degradation, MEP degradation, deoxyxylulose phosphate pathway, DXP pathway, Rohmer pathway, isopentenyl diphosphate biosynthesis – mevalonate-independent

Arabidopsis thaliana col , Escherichia coli K-12 , Lycopersicon esculentum

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