Page last updated: 2024-10-24

isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of isopentenyl diphosphate by the mevalonate-independent pathway. Isopentenyl diphosphate (IPP) is the fundamental unit in isoprenoid biosynthesis and is biosynthesized from pyruvate and glyceraldehyde 3-phosphate via intermediates, including 1-deoxy-D-xylulose 5-phosphate. [GOC:go_curators, MetaCyc:NONMEVIPP-PWY, PMID:18948055]

The methylerythritol 4-phosphate (MEP) pathway, also known as the non-mevalonate pathway, is a metabolic route that synthesizes isopentenyl diphosphate (IPP), a precursor to isoprenoids. This pathway is found in bacteria, plants, and some protists, but not in animals.

The MEP pathway starts with pyruvate and glyceraldehyde 3-phosphate, which are condensed to form 1-deoxy-D-xylulose 5-phosphate (DXP). DXP is then converted to MEP in a series of enzymatic steps. MEP is then phosphorylated to form methylerythritol 4-phosphate cytidyl diphosphate (CDP-MEP). CDP-MEP is then converted to 4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) through a complex series of reactions. Finally, HMBPP is decarboxylated to form IPP, which is then used in the biosynthesis of a wide variety of isoprenoids.

**Detailed steps in the MEP pathway:**

1. **Formation of 1-deoxy-D-xylulose 5-phosphate (DXP):** Pyruvate and glyceraldehyde 3-phosphate are condensed by the enzyme DXP synthase to form DXP.

2. **Formation of methylerythritol 4-phosphate (MEP):** DXP is then converted to MEP in a series of steps catalyzed by the enzymes DXP reductoisomerase, MEP synthase, and 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase.

3. **Formation of methylerythritol 4-phosphate cytidyl diphosphate (CDP-MEP):** MEP is phosphorylated by MEP kinase to form MEP 4-phosphate. MEP 4-phosphate is then reacted with CTP (cytidine triphosphate) by CDP-MEP synthase to form CDP-MEP.

4. **Formation of 4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP):** CDP-MEP is converted to HMBPP through a series of complex reactions catalyzed by the enzymes 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase and HMBPP synthase.

5. **Formation of isopentenyl diphosphate (IPP):** HMBPP is decarboxylated by the enzyme HMBPP reductase to form IPP.

**Importance of the MEP pathway:**

The MEP pathway is essential for the biosynthesis of isoprenoids, which are a diverse class of organic molecules with a wide range of biological functions. These functions include:

* **Hormone biosynthesis:** Many plant hormones, such as gibberellins, are isoprenoids.
* **Pigmentation:** Carotenoids, which are responsible for the yellow, orange, and red colors of many plants and animals, are isoprenoids.
* **Membrane structure:** Isoprenoids are important components of cell membranes.
* **Secondary metabolism:** Isoprenoids are involved in the production of a variety of secondary metabolites, such as terpenoids, steroids, and rubber.

**Applications of the MEP pathway:**

The MEP pathway has several potential applications, including:

* **Biotechnology:** The MEP pathway can be used to produce isoprenoids for use in various industries, such as pharmaceuticals, cosmetics, and food.
* **Agriculture:** The MEP pathway can be manipulated to improve the yield and quality of crops.
* **Medicine:** The MEP pathway is a potential target for the development of new drugs to treat diseases such as malaria and cancer.'
"

Proteins (5)

ProteinDefinitionTaxonomy
1-deoxy-D-xylulose-5-phosphate synthaseA 1-deoxy-D-xylulose-5-phosphate synthase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P77488]Escherichia coli K-12
1-deoxy-D-xylulose-5-phosphate synthaseA 1-deoxy-D-xylulose-5-phosphate synthase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P77488]Escherichia coli K-12
2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthaseA 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P62617]Escherichia coli K-12
1-deoxy-D-xylulose 5-phosphate reductoisomeraseA 1-deoxy-D-xylulose 5-phosphate reductoisomerase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P45568]Escherichia coli K-12
1-deoxy-D-xylulose 5-phosphate reductoisomeraseA 1-deoxy-D-xylulose 5-phosphate reductoisomerase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P45568]Escherichia coli K-12

Compounds (19)

CompoundDefinitionClassesRoles
fosmidomycinfosmidomycin : Propylphosphonic acid in which one of the hydrogens at position 3 is substituted by a formyl(hydroxy)amino group. An antibiotic obtained from Streptomyces lavendulae, it specifically inhibits DXP reductoisomerase (EC 1.1.1.267), a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis.

fosmidomycin: from Streptomyces lavendulae; RN given refers to parent cpd; structure in second source
hydroxamic acid;
phosphonic acids
antimicrobial agent;
bacterial metabolite;
EC 1.1.1.267 (1-deoxy-D-xylulose-5-phosphate reductoisomerase) inhibitor
cytidine diphosphateCytidine Diphosphate: Cytidine 5'-(trihydrogen diphosphate). A cytosine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: CRPP; cytidine pyrophosphate.cytidine 5'-phosphate;
pyrimidine ribonucleoside 5'-diphosphate
Escherichia coli metabolite;
mouse metabolite
1-nitroso-2-naphtholnaphthols
4-nitrosodimethylaniline4-nitrosodimethylaniline: structure; RN given refers to parent cpd

N,N-dimethyl-4-nitrosoaniline : A member of the class of dimethylanilines that is N,N-dimethylaniline having a nitroso group at the 4-position.
dimethylaniline;
nitroso compound;
tertiary amino compound
nitrosobenzenebenzenes;
nitroso compound
xenobiotic metabolite
2-nitrosotoluene
5-fluorocytidine5-fluorocytidine: isolated from DNA of Escherichia coli grown in presence of 5-fluorouracil; structure; RN given refers to parent cpdcytidines;
organofluorine compound
cyclic cmp3',5'-cyclic CMP : A 3',5'-cyclic pyrimidine nucleotide having cytosine as the nucleobase.

Cyclic CMP: A cyclic nucleotide formed from CYTIDINE TRIPHOSPHATE by the action of cytidylate cyclase. It is a potential cyclic nucleotide intracellular mediator of signal transductions.
3',5'-cyclic pyrimidine nucleotidehuman metabolite
cidofovir anhydrouscidofovir anhydrous : Cytosine substituted at the 1 position by a 3-hydroxy-2-(phosphonomethoxy)propyl group (S configuration). A nucleoside analogue, it is an injectable antiviral used for the treatment of cytomegalovirus (CMV) retinitis in AIDS patients.

Cidofovir: An acyclic nucleoside phosphonate that acts as a competitive inhibitor of viral DNA polymerases. It is used in the treatment of RETINITIS caused by CYTOMEGALOVIRUS INFECTIONS and may also be useful for treating HERPESVIRUS INFECTIONS.
phosphonic acids;
pyrimidone
anti-HIV agent;
antineoplastic agent;
antiviral drug;
photosensitizing agent
1-beta-d-arabinofuranosylcytosine 5'-monophosphate1-beta-D-arabinofuranosylcytosine 5'-monophosphate: RN given refers to dihydrogen phosphate
3-aminopropylphosphonic acid(3-aminopropyl)phosphonic acid : A phosphonic acid in which the hydrogen attached to the phosphorus of phosphonic acid is substituted by a 3-aminopropyl group. It is a partial agonist of GABAB receptors.

3-aminopropylphosphonic acid: RN given refers to parent cpd; structure
phosphonic acids;
primary amino compound;
zwitterion
GABAB receptor agonist
n-hydroxy-4-phosphonobutanamideN-hydroxy-4-phosphonobutanamide: structure given in first source
3-(n-acetyl-n-hydroxy)aminopropylphosphonic acid3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid: from Streptomyces rubellomurinus sp. nov.; interferes with bacterial cell wall synthesis; structure in first sourcephosphonoacetic acid
fosmidomycin monosodium salt
quercetin7-hydroxyflavonol;
pentahydroxyflavone
antibacterial agent;
antineoplastic agent;
antioxidant;
Aurora kinase inhibitor;
chelator;
EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor;
geroprotector;
phytoestrogen;
plant metabolite;
protein kinase inhibitor;
radical scavenger
luteolin3'-hydroxyflavonoid;
tetrahydroxyflavone
angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
c-Jun N-terminal kinase inhibitor;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
immunomodulator;
nephroprotective agent;
plant metabolite;
radical scavenger;
vascular endothelial growth factor receptor antagonist
baicaleintrihydroxyflavoneangiogenesis inhibitor;
anti-inflammatory agent;
antibacterial agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 1.13.11.31 (arachidonate 12-lipoxygenase) inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
EC 4.1.1.17 (ornithine decarboxylase) inhibitor;
ferroptosis inhibitor;
geroprotector;
hormone antagonist;
plant metabolite;
prostaglandin antagonist;
radical scavenger
fisetin3'-hydroxyflavonoid;
7-hydroxyflavonol;
tetrahydroxyflavone
anti-inflammatory agent;
antioxidant;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
geroprotector;
metabolite;
plant metabolite
myricetin7-hydroxyflavonol;
hexahydroxyflavone
antineoplastic agent;
antioxidant;
cyclooxygenase 1 inhibitor;
food component;
geroprotector;
hypoglycemic agent;
plant metabolite