MilliporeSigma
HomeMetabolomics ResearchIsoprene Biosynthesis

Isoprene Biosynthesis

The 5-carbon isomers isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) are the fundamental building blocks used to synthesize key biological isoprenoids (terpenoids) including cholesterol and other steroids, carotenoids, saponins, and limonoids.

Two metabolic pathways exist for the biosynthesis of isopentenyl pyrophosphate and dimethylallyl pyrophosphate:

  • The mevalonate pathway, predominantly used by plants and in a few insect species
  • The non-mevalonate pathway or methyl D-erythritol 4-phosphate (MEP) pathway, which occurs in plant chloroplasts, algae, cyanobacteria, eubacteria, and important pathogens such as Mycobacterium tuberculosis and malaria parasites
Isoprene Biosynthesis

Figure 1.Isoprene biosynthesis.

Mevalonate Pathway

The mevalonate pathway performs several key functions within cells and is an important central metabolic pathway in all higher eukaryotic cells. The key isomers dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) are produced via the mevalonate pathway from (R)-mevalonate and its subsequent phosphorylated metabolites (R)-mevalonate-5-phosphate and (R)-mevalonate-pyrophosphate.

DMAPP and IPP are further utilized in condensation reactions for the biosynthesis of isoprenoids. These isoprenoids are transformed to more complex, cyclised structures through steroid and terpenoid biosynthesis and are involved in protein prenylation and protein anchoring. Mechanisms for feedback regulation of low-density lipoprotein receptors and enzymes involved in mevalonate biosynthesis ensure that sufficient mevalonate is available to generate the required quantity of DMAPP and IPP. The mevalonate pathway is of biomedical interest in certain types of cancer as well as heart disease, and a number of therapeutic drugs target this regulatory system.

Non-mevalonate (MEP) Pathway

The mevalonate-independent pathway for the biosynthesis of IPP and DMAPP was discovered in the 1990’s and consists of eight enzyme-catalyzed reactions. Synonyms for this pathway are the non-mevalonate pathway, the 1-deoxy-D-xylulose-5-phosphate pathway (DXP (or DOXP) pathway), and the 2C-methyl-D-erythritol-4-phosphate pathway, (MEP pathway).

The MEP pathway starts with the condensation of pyruvate and D-glyceraldehyde-3-phosphate to 1-deoxy-D-xylulose-5-phosphate (DXP or DOXP). The key isomers DMAPP and IPP are subsequently formed via a series of enzymatic steps starting with the conversion of DXP to 2C-methyl-D-erythritol-4-phosphate (MEP). Enzymes of this MEP pathway are attractive targets for the development of drugs targeting infectious diseases such as malaria and tuberculosis, because this pathway occurs in pathogenic prokaryotes but is absent in human metabolic pathways.

Table 1.Mevalonic pathway metabolites.
Table 2.Non-mevalonate pathway metabolites.