Non-mevalonate pathway

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).

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 that serve as the basis for the biosynthesis of molecules used in processes as diverse as protein prenylation, cell membrane maintenance, hormones, protein anchoring and N-glycosylation.

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 Mycobacterium tuberculosis synthesize IPP and DMAPP via the non-mevalonate pathway.

The reactions are as follows:

Fosmidomycin specifically inhibits DOXP reductoisomerase, a key enzyme in the non-mevalonate pathway, and therefore represents an attractive candidate as antibiotic or antimalarial drug.

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