1- Hydroxy-2-methyl-2-butenyl 4-diphosphate

Figure 11 Biosynthesis of isoprenoid type cofactors. 18, Heme a 39, pyridoxal 5 -phosphate 43, 1-deoxy-D-xylulose 5-phosphate 46, thiamine pyrophosphate 83, acetyl-CoA 84, (S)-3-hydroxy-3-methylglutaryl-CoA 85, mevalonate 86, isopentenyl diphosphate (IPP) 87, dimethylallyl diphosphate (DMAPP) 88, pyruvate 89, D-glyceraldehyde 3-phosphate 90, 2C-methyl-D-erythritol 4-phosphate 91, 2C-methyl-erythritol 2,4-cyclodiphosphate 92, 1-hydroxy-2-methyl-2-( )-butenyl 4-diphosphate 93, polyprenyl diphosphate 94, cholecalciferol 95, fS-carotene 96, retinol 97, ubiquinone 98, menaquinone 99, a-tocopherol.

Finally, a two electron reduction of cMEPP forms 2-methyl-2-( )-butenyl diphosphate followed by conversion to IPP and DMAPP. These steps are catalyzed by 1 -hydroxy-2-methyl-2-( )-butenyl-4-diphosphate synthase (IspG) [26] and 4-hydroxy-3-methyl-2-( )-butenyl-4-diphosphate reductase (IspH) [27], respectively. IspG and IspH enzymes possess [4Fe-4S] iron-sulfur redox cluster in their C-terminal domains, which represents the active center of the enzymes. The newest cocrystal structures of IspH from E. coli revealed the presence of a [4Fe-4S] cluster... 

The biosynthetic pathway producing isoprenoid cytokinins has been identified, whereas that of aromatic cytokinins is poorly characterized.363 385 Two distinct pathways for isoprenoid cytokinin biosynthesis have been described, and each pathway employs a different type of isopentenyltransferase at the initial step. The major pathway in higher plants, which is catalyzed by IPT, is conjugation of adenine nucleotide and DMAPP or 4-hydroxy-3-methyl-2-( )-butenyl diphosphate (HMBDP) (Figure 14). In the less frequently used pathway, cytokinins are formed by degradation of prenylated tRNAs. The initial prenylation reaction of tRNA is catalyzed by tRNA-isopentenyltransferase (tRNA-IPT) (Figure 14). 

C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-cPP) l-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBPP)... 

Usually, the MEP/DOXP pathway in plastids is responsible for the production of essential oil monoterpenes and linalyl acetate, some sesquiterpenes, diterpenes, and carotenoids and phytol. A number of dmgs target the mevalonate pathway, for example, fosmidomycin specifically inhibits DOXP reductoisomerase, a committed enzyme in the non-mevalonate pathway. In addition, the intermediate 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBDP) is the namral activator for human Vy9/V 2 T cells, the major T-cell population in peripheral blood. 

Fig. 15.2 Biosynthetic pathway of ubiquinone in prokaryotes. Enzyme names and intermediates are inferred from research studies in E. coli. The chain length of isoprenoids tmd ubiquinone pathway intermediates is kept unspecified (n) to generalize the pathway model to encompass all prokaryotes. (1) eiythtose-4-phosphate (2) phosphoenolpyruvate (3) 3-deoxy-ttfabino-heptulosonate 7-phosphate (4) 3-dehydroquinate (5) 3-dehydroshikimate (6) shikimate (7) shikimate-3-phos-phate (8) 5-enolpyruvyl-shikimate-3-phosphate (9) chorismate (10) para hydroxybenzoate (11) pyruvate (12) glyceraldehyde-3-phosphate (13) l-deoxy-D-xyMose-5-phosphate (14) 2-C-methyl-D-eiythrithol-5-phosphate (15) 4-diphosphocytidyl-2C-methyl-D-erythritol (16) 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate (17) 2-C-methyl-D-erythritol-2,4-cyclo-diphosphate (18) l-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (19) demethylaUyl diphosphate (20) isopentenyl diphosphate (21) farnesyl diphosphate (22) polyprenyl diphosphate (23) 3-polyprenyl-4-hydrobenzoate (24) 2-polyprenylphenol (25) 2-polypienyl-6-hydtoxyphenol ...

Adam, R, Hecht, S., Eisenreich, W.G. et al. (2002) Biosynthesis of terpenes studies on l-hydroxy-2-methyl-2-( )-butenyl 4-diphosphate reductase. Proc. Natl. Acad. Sci. USA, 99, 12108-12113. 

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