DOXP reductoisomerase

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. 

The diethyl esters (466) and disodium salts (467) of a range of hetero-arylcarbamoylphosphonic acids have been prepared from (465) and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor fosmidomycin. A number of synthetic ligands has been shown to exhibit both enzyme-binding and enzyme-inhibition activity (Scheme 115). ... 

As seen in Fig. 18.1, the MEP/DOXP pathway initiates as l-deoxy-o-xylulose 5-phos-phate is synthesized from pyruvate and D-glyceraldehyde-3P (both from the glycolysis/glucogenesis pathway) formed by the enzyme l-deoxy-D-xylulose-5-phosphate S5mthase (DXS, EC 2.2.1.7). The l-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR, EC 1.1.1.267) then catalyzes the formation of MEP. In later steps, IPP is formed from MEP via a series of reactions involving several reductases, dehydratases, a kinase, and cofactors (Lichtenthaler, 1999). Based on the identified enzymes (Table 18.1) and metabolic pathways. 

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