The non-mevalonate pathway—also appearing as the mevalonate-independent pathway and the 2-C-methyl--erythritol 4-phosphate/1-deoxy--xylulose 5-phosphate (MEP/DOXP) pathway—is an alternative metabolic pathway for isoprenoid biosynthesis that forms isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP).
Contents
Diversity of isoprenoid biosynthesis
The classical mevalonate pathway or HMG-CoA reductase pathway is an important cellular metabolic pathway present in all higher eukaryotes and some bacteria. It is important for the production of IPP and DMAPP, which serve as the basis for the biosynthesis of molecules used in processes as diverse as protein prenylation, cell membrane maintenance, hormone synthesis, protein anchoring and N-glycosylation.
In contrast to the classical mevalonate pathway of isoprenoid biosynthesis, bacteria, plants, and apicomplexan protozoa—such as malaria parasites—are able to produce isoprenoids (including the dimeric isoprenoids, the terpenoids) using an alternative pathway, the non-mevalonate pathway; in the case of the eukaryotic protozoans and plants, the biosynthesis takes place in their plastid organelles. Bacteria that use the pathway include important pathogens such Mycobacterium tuberculosis.
Reactions
The reactions of the non-mevalonate pathway are as follows, taken primarily from Eisenreich and co-workers, except where the bold labels are additional local abbreviations to assist in connecting the table to the scheme above:
Inhibition and other pathway research
DOXP reductoisomerase (DXP reductoisomerase, MAP synthase), a key enzyme in the non-mevalonate pathway, is inhibited a natural product, fosmidomycin, which is under study as a starting point to develop a candidate antibacterial or antimalarial drug.
The intermediate, HMB-PP, is a natural activator of human Vγ9/Vδ2 T cells, the major γδ T cell population in peripheral blood, and cells that "play a crucial role in the immune response to microbial pathogens".