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Escherichia coli K-12 substr. MG1655 Pathway: superpathway of histidine, purine, and pyrimidine biosynthesis

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:
















If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

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Synonyms: nonmevalonate isopentenyl diphosphate biosynthesis, methylerythritol degradation

, Pathway Summary from MetaCyc: General Background

The biosynthesis of isopentenyl diphosphate Subpathways: (IPP) can occur via two distinct routes: the guanosine ribonucleotides de novo biosynthesis , guanosine deoxyribonucleotides onMouseOver="return overlib('Pathway: mevalonate pathway I
Synonyms: isoprenoid pathway, MVA pathway, isopentenyl diphosphate biosynthesis,
  dimethylallyl diphosphate biosynthesis', WIDTH, 419);" onmouseout="return nd();">de novo biosynthesis IImevalonate pathway I
, (MVA pathway) and the 5-aminoimidazole ribonucleotide biosynthesis II , inosine-5'-phosphate biosynthesis I , superpathway of guanosine nucleotides de novo biosynthesis II , onMouseOver="return overlib('Pathway: methylerythritol phosphate pathway I
Synonyms: nonmevalonate isopentenyl diphosphate biosynthesis, methylerythritol phosphate degradation,
  MEP degradation, deoxyxylulose phosphate pathway, DOXP pathway, Rohmer pathway,
  isopentenyl diphosphate biosynthesis -- mevalonate-independent,
  nonmevalonate isoprenoid pathway, MEP pathway', WIDTH, 500);" onmouseout="return nd();"> methylerythritol phosphate pathway Isuperpathway of adenosine nucleotides (MEP pathway, this pathway) de novo biosynthesis II , adenosine deoxyribonucleotides de novo biosynthesis II , [adenosine ribonucleotides de novo biosynthesis , histidine biosynthesis onMouseOver="return overlib(' Lange BM, Rujan T, Martin W, Croteau R (2000). "Isoprenoid biosynthesis: the evolution of two ancient and distinct pathways across genomes." Proc Natl Acad Sci U S A 97(24);13172-7. PMID: 11078528', WIDTH, 500);" onmouseout="return nd();">, Lange00]superpathway of purine nucleotides de novo biosynthesis II , . In the former, IPP is synthesized from the condensation of three acetyl-CoA molecules; in the MEP pathway IPP is synthesized via the condensation of PRPP biosynthesis I , PRPP biosynthesis II , onMouseOver="return overlib('Compound: pyruvate
Synonyms: alpha-ketopropionic acid, BTS, α-ketopropionic acid, acetylformic acid,
  pyroracemic acid, 2-oxopropanoic acid, pyruvic acid, 2-oxopropanoate,
  2-oxo-propionic acid', WIDTH, 399);" onmouseout="return nd();">superpathway of pyrimidine ribonucleotides pyruvate
de novo biosynthesis , and UTP and CTP de novo biosynthesis , UMP biosynthesis D-glyceraldehyde 3-phosphate.

For many years, the MVA pathway was considered to be the sole source of IPP in all living organisms. However, several inconsistencies led to the discovery of the MEP pathway in bacteria and plants. In plants the MVA pathway is located in the cytosol whilst the MEP pathway is found in plastids [Lichtenthaler97]. The MEP pathway is present in most eubacteria, unicellular green algae, the chloroplasts of phototrophic organisms and some unicellular eukaryotes related to photosynthetic phyla, such as the Plasmodium parasites [Kuntz05].

About This Pathway

Isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP) are the fundamental units in isoprenoid biosynthesis. Both are produced from D-glyceraldehyde 3-phosphate and pyruvate via this pathway.

D-glyceraldehyde-3-phosphate and pyruvate are initially combined to yield 1-deoxy-D-xylulose 5-phosphate (DOXP). DOXP is then rearranged and reduced to generate the pathway's namesake compound, 2-C-methyl-D-erythritol 4-phosphate (MEP). Interestingly, two rather different enzymes, that share no sequence homology, are able to catalyze this reaction - the DXR enzymes, and the DRL (DXR-like) enzymes [Sangari10].

In the third reaction MEP is converted into 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol, which is subsequently phosphorylated at the 2 position hydroxy group, yielding 2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. This product is then converted into 2-C-methyl-D-erythritol-2,4-cyclodiphosphate. Subsequently, it is reduced to generate 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate [Adam02].

This diphosphate compound is converted by a single enzyme into a 5-6:1 ratio of IPP and DMAPP in the final step. In Escherichia coli this ratio is subsequently adjusted to 3:7 by isopentenyl diphosphate isomerase. IPP and DMAPP serve as the basic building blocks of polyisoprenoid biosynthesis.

The difference between this pathway variant and the variant described in methylerythritol phosphate pathway II is the conversion of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate to 2-C-methyl-D-erythritol-2,4-cyclodiphosphate. In this variant, that enzyme utilizes flavodoxin as the electron donor (EC 1.17.7.b, (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (flavodoxin)), while in the other variant the enzyme utilizes ferredoxin (EC 1.17.7.1, (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (ferredoxin)).

This pathway, which is not present in humans, is involved in production of phosphate-containing antigens recognized by γ-δ T lymphocytes [Feurle02]. Variants: mevalonate pathway Pathway Evidence Glyph: MEP degradation

Superclasses: Superpathways
Summary: Superclasses: Pyrimidine, purine, and pyridine nucleotide synthesis all require phosphoribosylpyrophosphate (PRPP) as a precursor. PRPP is utilized by both the de novo pathways and the auxiliary or salvage pathways by which endogenously formed or exogenously added pyrimidine, purine, or pyridine bases are converted to the corresponding ribonucleoside monophosphates by phosphoribosyltransferases. PRPP is also used in the histidine and tryptophan biosynthesis pathways. PRPP thus may be regarded as a precursor for the synthesis of nucleic acids, proteins, and for the NAD(P) coenzymes.The formation of PRPP therefore is subjected to strict metabolic control. Biosynthesis Secondary Metabolites Biosynthesis [ → Terpenoids Biosynthesis onMouseOver="return overlib(' Hove-Jensen B, Harlow KW, King CJ, Switzer RL (1986). "Phosphoribosylpyrophosphate synthetase of Escherichia coli. Properties of the purified enzyme and primary structure of the prs gene." J Biol Chem 1986;261(15);6765-71. PMID: 3009477', WIDTH, 500);" onmouseout="return nd();">Hemiterpenes Biosynthesis HoveJensen86] → Isopentenyl Diphosphate Biosynthesis


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Sun Mar 1, 2015, biocyc14.