The non-mevalonate pathway or 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway (MEP/DOXP pathway) of isoprenoid biosynthesis is an alternative metabolic pathway leading to the formation of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) that has been elucidated only recently.
In contrast to the classical mevalonate pathway of isoprenoid biosynthesis, plants and apicomplexan protozoa such as malaria parasites have the ability to produce their isoprenoids (terpenoids) using an alternative pathway, the non-mevalonate pathway, which takes place in their plastids. In addition, most bacteria including important pathogens such as Mycobacterium tuberculosis synthesize IPP and DMAPP via the non-mevalonate pathway.
|Pyruvate and glyceraldehyde 3-phosphate||DOXP synthase (Dxs)||1-Deoxy-D-xylulose 5-phosphate (DOXP)|
|DOXP||DOXP reductase (Dxr, IspC)||2-C-methylerythritol 4-phosphate (MEP)|
|MEP||4-diphosphocytidyl-2-C-methyl-D-erythritol synthase (YgbP, IspD)||4-diphosphocytidyl-2-C-methylerythritol (CDP-ME)|
|CDP-ME||4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (YchB, IspE)||4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-MEP)|
|CDP-MEP||2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (YgbB, IspF)||2-C-methyl-D-erythritol 2,4-cyclopyrophosphate (MEcPP)|
|MEcPP||HMB-PP synthase (GcpE, IspG)||(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP)|
|HMB-PP||HMB-PP reductase (LytB, IspH)||IPP and DMAPP|
Anti-malarial drug targets: screening for inhibitors of 2C-methyl-D-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants.
Apr 01, 2007; Abstract The recently discovered non-mevalonate pathway of isoprenoid biosynthesis serves as the unique source of terpenoids in...