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

Isopentenyl pyrophosphate

Isopentenyl pyrophosphate is an intermediate in the classical, HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes and terpenoids. IPP is formed from acetyl-CoA via mevalonic acid...

 (IPP) and dimethylallyl pyrophosphate

Dimethylallyl pyrophosphate

Dimethylallyl pyrophosphate is an intermediate product of both mevalonic acid pathway and DOXP/MEP pathway. It is an isomer of isopentenyl pyrophosphate and exists in virtually all life forms...

 (DMAPP) that has been elucidated only recently.

Diversity of isoprenoid biosynthesis

The classical mevalonate pathway or HMG-CoA reductase

HMG-CoA reductase

HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids...

 pathway is an important cellular metabolic pathway present in all higher eukaryotes and many 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

Prenylation

Prenylation, or isoprenylation, or lipidation is the addition of hydrophobic molecules to a protein. It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing...

, cell membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 maintenance, hormones, protein anchoring

Lipid anchored protein

In lipid-anchored proteins, a covalently attached fatty acid such as palmitate or myristate serves to anchor them to either face of the cell membrane. Examples include G proteins and certain kinases. It is believed that the fatty acid chain inserts and assumes a place in the bilayer structure of...

 and N-glycosylation

Glycosylation

Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...

.

In contrast to the classical mevalonate pathway of isoprenoid biosynthesis, plant

Plant

Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

s and apicomplexa

Apicomplexa

The Apicomplexa are a large group of protists, most of which possess a unique organelle called apicoplast and an apical complex structure involved in penetrating a host's cell. They are unicellular, spore-forming, and exclusively parasites of animals. Motile structures such as flagella or...

n protozoa

Protozoa

Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...

 such as malaria

Malaria

Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

 parasites have the ability to produce their isoprenoids (terpenoids) using an alternative pathway, the non-mevalonate pathway, which takes place in their plastid

Plastid

Plastids are major organelles found in the cells of plants and algae. Plastids are the site of manufacture and storage of important chemical compounds used by the cell...

s. In addition, most bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 including important pathogens such as Mycobacterium tuberculosis

Mycobacterium tuberculosis

Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

synthesize IPP and DMAPP via the non-mevalonate pathway.

Reactions

The reactions are as follows:

Reactants

Enzyme

Product >- | Pyruvate and glyceraldehyde 3-phosphate Glyceraldehyde 3-phosphate Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GADP, GAP, TP, GALP or PGAL, is a chemical compound that occurs as an intermediate in several central metabolic pathways of all organisms...

DOXP synthase (Dxs)

1-Deoxy-D-xylulose 5-phosphate 1-Deoxy-D-xylulose 5-phosphate 1-Deoxy-D-xylulose 5-phosphate is an intermediate in the non-mevalonate pathway.-See also:* DXP synthase* DXP reductoisomerase...  (DOXP)

>- | DOXP

DOXP reductase (Dxr, IspC)

2-C-methylerythritol 4-phosphate 2-C-methylerythritol 4-phosphate 2-C-Methylerythritol 4-phosphate is an intermediate in the non-mevalonate pathway....  (MEP)

>- | MEP

4-diphosphocytidyl-2-C-methyl-D-erythritol synthase (YgbP, IspD)

4-diphosphocytidyl-2-C-methylerythritol 4-Diphosphocytidyl-2-C-methylerythritol 4-Diphosphocytidyl-2-C-methylerythritol is an intermediate in the non-mevalonate pathway....  (CDP-ME)

>- | CDP-ME

4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (YchB, IspE)

4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate 4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate 4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate is an intermediate in the non-mevalonate pathway.It is formed by CDP-ME kinase....  (CDP-MEP)

>- | CDP-MEP

2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase In enzymology, a 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase is an enzyme is a lyase which participates in biosynthesis of steroids. It catalyzes the chemical reaction:...  (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 (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate -4-Hydroxy-3-methyl-but-2-enyl pyrophosphate is an intermediate of the non-mevalonate pathway of isoprenoid biosynthesis...  (HMB-PP)

>- | HMB-PP

HMB-PP reductase (LytB, IspH)

IPP Isopentenyl pyrophosphate Isopentenyl pyrophosphate is an intermediate in the classical, HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes and terpenoids. IPP is formed from acetyl-CoA via mevalonic acid...  and DMAPP Dimethylallyl pyrophosphate Dimethylallyl pyrophosphate is an intermediate product of both mevalonic acid pathway and DOXP/MEP pathway. It is an isomer of isopentenyl pyrophosphate and exists in virtually all life forms...

Inhibition

Fosmidomycin

Fosmidomycin

Fosmidomycin is an antibiotic that was originally isolated from culture broths of bacteria of the genus Streptomyces. It specifically inhibits DXP reductoisomerase, a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. It is a structural analogue of 2-C-methyl-D-erythrose...

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

T cell activation

The intermediate HMB-PP is the natural activator for human Vγ9/Vδ2 T cells, the major γδ T cell population in peripheral blood.