methylerythritol phosphate pathway I
MetaCyc:NONMEVIPP-PWY
The methylerythritol phosphate (MEP/DOXP) route converts pyruvate and D-glyceraldehyde 3-phosphate to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). This record represents the Escherichia coli K-12 enzyme set; the native MetaCyc pathway also lists K-12 MG1655 and Brucella abortus. IspH directly supplies both products; Idi is an additional interconversion, not an obligatory route to DMAPP. Variant I uses flavodoxin for IspG. Current Rhea IspH equations use generic ferredoxin, whereas primary E. coli assays support flavodoxin-dependent activation; unresolved carrier-state edges are omitted. This partial chemical graph is not a stoichiometric flux model, and source reaction directions do not imply irreversibility.
- Pathway type
- isoprenoid precursor biosynthesis
- Organism scope
Pathway network
44 nodes · 68 asserted directed edges
Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.
- Reaction / activity
- Chemical / cofactor
- Protein / complex
- Cell / process context
- Solid arrow: mechanistic relation
- Dashed arrow: membership, location or cofactor relation
Components and activities
| Node | Kind or role | Source direction |
|---|---|---|
Escherichia coli K-12NCBITaxon:83333 | taxon | |
D-glyceraldehyde 3-phosphateCHEBI:59776 | small molecule | |
pyruvateCHEBI:15361 | small molecule | |
H(+)CHEBI:15378 | small molecule | |
1-deoxy-D-xylulose 5-phosphateCHEBI:57792 | small molecule | |
CO2CHEBI:16526 | small molecule | |
1-deoxy-D-xylulose-5-phosphate synthaseUniProtKB:P77488 | protein | |
NADPHCHEBI:57783 | small molecule | |
2-C-methyl-D-erythritol 4-phosphateCHEBI:58262 | small molecule | |
NADP(+)CHEBI:58349 | small molecule | |
1-deoxy-D-xylulose 5-phosphate reductoisomeraseUniProtKB:P45568 | protein | |
CTPCHEBI:37563 | small molecule | |
4-CDP-2-C-methyl-D-erythritolCHEBI:57823 | small molecule | |
diphosphateCHEBI:33019 | small molecule | |
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferaseUniProtKB:Q46893 | protein | |
ATPCHEBI:30616 | small molecule | |
4-CDP-2-C-methyl-D-erythritol 2-phosphateCHEBI:57919 | small molecule | |
ADPCHEBI:456216 | small molecule | |
4-diphosphocytidyl-2-C-methyl-D-erythritol kinaseUniProtKB:P62615 | protein | |
2-C-methyl-D-erythritol 2,4-cyclic diphosphateCHEBI:58483 | small molecule | |
CMPCHEBI:60377 | small molecule | |
2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthaseUniProtKB:P62617 | protein | |
(2E)-4-hydroxy-3-methylbut-2-enyl diphosphateCHEBI:128753 | small molecule | |
H2OCHEBI:15377 | small molecule | |
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin)UniProtKB:P62620 | protein | |
isopentenyl diphosphateCHEBI:128769 | small molecule | |
4-hydroxy-3-methylbut-2-enyl diphosphate reductaseUniProtKB:P62623 | protein | |
dimethylallyl diphosphateCHEBI:57623 | small molecule | |
Isopentenyl-diphosphate Delta-isomeraseUniProtKB:Q46822 | protein | |
Mg(2+)CHEBI:18420 | cofactor | |
thiamine diphosphateCHEBI:58937 | cofactor | |
Mn(2+)CHEBI:29035 | cofactor | |
Co(2+)CHEBI:48828 | cofactor | |
a divalent metal cationCHEBI:60240 | cofactor | |
[4Fe-4S] clusterCHEBI:49883 | cofactor | |
cytoplasmGO:0005737 | cellular component | |
Dxs condensation to 1-deoxy-D-xylulose 5-phosphateRHEA:12606 | reaction | left to right |
Dxr rearrangement and reduction to MEPRHEA:13719 | reaction | right to left |
IspD cytidylylation of MEPRHEA:13430 | reaction | left to right |
IspE phosphorylation of CDP-MERHEA:18438 | reaction | left to right |
IspF formation of methylerythritol cyclic diphosphateRHEA:23865 | reaction | left to right |
IspG reduction to HMBPP (flavodoxin reaction family)RHEA:43606 | reaction | right to left |
IspH HMBPP reduction to IPP (chemical-side projection)RHEA:24490 | reaction | right to left |
IspH HMBPP reduction to DMAPP (chemical-side projection)RHEA:24827 | reaction | right to left |
Idi interconversion of IPP to DMAPPRHEA:23285 | reaction | left to right |
Mechanistic edges
| Subject | Predicate and description | Object | Evidence |
|---|---|---|---|
D-glyceraldehyde 3-phosphateCHEBI:59776 | consumes | Dxs condensation to 1-deoxy-D-xylulose 5-phosphateRHEA:12606 |
|
pyruvateCHEBI:15361 | consumes | Dxs condensation to 1-deoxy-D-xylulose 5-phosphateRHEA:12606 |
|
H(+)CHEBI:15378 | consumes | Dxs condensation to 1-deoxy-D-xylulose 5-phosphateRHEA:12606 |
|
Dxs condensation to 1-deoxy-D-xylulose 5-phosphateRHEA:12606 | produces | 1-deoxy-D-xylulose 5-phosphateCHEBI:57792 |
|
Dxs condensation to 1-deoxy-D-xylulose 5-phosphateRHEA:12606 | produces | CO2CHEBI:16526 |
|
1-deoxy-D-xylulose-5-phosphate synthaseUniProtKB:P77488 | catalyzes | Dxs condensation to 1-deoxy-D-xylulose 5-phosphateRHEA:12606 |
|
1-deoxy-D-xylulose 5-phosphateCHEBI:57792 | consumes | Dxr rearrangement and reduction to MEPRHEA:13719 |
|
NADPHCHEBI:57783 | consumes | Dxr rearrangement and reduction to MEPRHEA:13719 |
|
H(+)CHEBI:15378 | consumes | Dxr rearrangement and reduction to MEPRHEA:13719 |
|
Dxr rearrangement and reduction to MEPRHEA:13719 | produces | 2-C-methyl-D-erythritol 4-phosphateCHEBI:58262 |
|
Dxr rearrangement and reduction to MEPRHEA:13719 | produces | NADP(+)CHEBI:58349 |
|
1-deoxy-D-xylulose 5-phosphate reductoisomeraseUniProtKB:P45568 | catalyzes | Dxr rearrangement and reduction to MEPRHEA:13719 |
|
2-C-methyl-D-erythritol 4-phosphateCHEBI:58262 | consumes | IspD cytidylylation of MEPRHEA:13430 |
|
CTPCHEBI:37563 | consumes | IspD cytidylylation of MEPRHEA:13430 |
|
H(+)CHEBI:15378 | consumes | IspD cytidylylation of MEPRHEA:13430 |
|
IspD cytidylylation of MEPRHEA:13430 | produces | 4-CDP-2-C-methyl-D-erythritolCHEBI:57823 |
|
IspD cytidylylation of MEPRHEA:13430 | produces | diphosphateCHEBI:33019 |
|
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferaseUniProtKB:Q46893 | catalyzes | IspD cytidylylation of MEPRHEA:13430 |
|
4-CDP-2-C-methyl-D-erythritolCHEBI:57823 | consumes | IspE phosphorylation of CDP-MERHEA:18438 |
|
ATPCHEBI:30616 | consumes | IspE phosphorylation of CDP-MERHEA:18438 |
|
IspE phosphorylation of CDP-MERHEA:18438 | produces | 4-CDP-2-C-methyl-D-erythritol 2-phosphateCHEBI:57919 |
|
IspE phosphorylation of CDP-MERHEA:18438 | produces | ADPCHEBI:456216 |
|
IspE phosphorylation of CDP-MERHEA:18438 | produces | H(+)CHEBI:15378 |
|
4-diphosphocytidyl-2-C-methyl-D-erythritol kinaseUniProtKB:P62615 | catalyzes | IspE phosphorylation of CDP-MERHEA:18438 |
|
4-CDP-2-C-methyl-D-erythritol 2-phosphateCHEBI:57919 | consumes | IspF formation of methylerythritol cyclic diphosphateRHEA:23865 |
|
IspF formation of methylerythritol cyclic diphosphateRHEA:23865 | produces | 2-C-methyl-D-erythritol 2,4-cyclic diphosphateCHEBI:58483 |
|
IspF formation of methylerythritol cyclic diphosphateRHEA:23865 | produces | CMPCHEBI:60377 |
|
2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthaseUniProtKB:P62617 | catalyzes | IspF formation of methylerythritol cyclic diphosphateRHEA:23865 |
|
2-C-methyl-D-erythritol 2,4-cyclic diphosphateCHEBI:58483 | consumes Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | IspG reduction to HMBPP (flavodoxin reaction family)RHEA:43606 |
|
IspG reduction to HMBPP (flavodoxin reaction family)RHEA:43606 | produces Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | (2E)-4-hydroxy-3-methylbut-2-enyl diphosphateCHEBI:128753 |
|
IspG reduction to HMBPP (flavodoxin reaction family)RHEA:43606 | produces Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | H2OCHEBI:15377 |
|
IspG reduction to HMBPP (flavodoxin reaction family)RHEA:43606 | produces Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | H(+)CHEBI:15378 |
|
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin)UniProtKB:P62620 | catalyzes | IspG reduction to HMBPP (flavodoxin reaction family)RHEA:43606 |
|
(2E)-4-hydroxy-3-methylbut-2-enyl diphosphateCHEBI:128753 | consumes Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | IspH HMBPP reduction to IPP (chemical-side projection)RHEA:24490 |
|
H(+)CHEBI:15378 | consumes Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | IspH HMBPP reduction to IPP (chemical-side projection)RHEA:24490 |
|
IspH HMBPP reduction to IPP (chemical-side projection)RHEA:24490 | produces Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | isopentenyl diphosphateCHEBI:128769 |
|
IspH HMBPP reduction to IPP (chemical-side projection)RHEA:24490 | produces Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | H2OCHEBI:15377 |
|
4-hydroxy-3-methylbut-2-enyl diphosphate reductaseUniProtKB:P62623 | catalyzes The supported IspH chemical conversion is retained. Its UniProt/Rhea generic ferredoxin equation does not establish the E. coli physiological donor; flavodoxin-dependent activation was observed in PMID:12571359. | IspH HMBPP reduction to IPP (chemical-side projection)RHEA:24490 |
|
(2E)-4-hydroxy-3-methylbut-2-enyl diphosphateCHEBI:128753 | consumes Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | IspH HMBPP reduction to DMAPP (chemical-side projection)RHEA:24827 |
|
H(+)CHEBI:15378 | consumes Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | IspH HMBPP reduction to DMAPP (chemical-side projection)RHEA:24827 |
|
IspH HMBPP reduction to DMAPP (chemical-side projection)RHEA:24827 | produces Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | dimethylallyl diphosphateCHEBI:57623 |
|
IspH HMBPP reduction to DMAPP (chemical-side projection)RHEA:24827 | produces Chemical-side projection only: source generic electron-carrier states are not represented. This edge does not establish a balanced complete reaction or the physiological donor identity. | H2OCHEBI:15377 |
|
4-hydroxy-3-methylbut-2-enyl diphosphate reductaseUniProtKB:P62623 | catalyzes The supported IspH chemical conversion is retained. Its UniProt/Rhea generic ferredoxin equation does not establish the E. coli physiological donor; flavodoxin-dependent activation was observed in PMID:12571359. | IspH HMBPP reduction to DMAPP (chemical-side projection)RHEA:24827 |
|
isopentenyl diphosphateCHEBI:128769 | consumes | Idi interconversion of IPP to DMAPPRHEA:23285 |
|
Idi interconversion of IPP to DMAPPRHEA:23285 | produces | dimethylallyl diphosphateCHEBI:57623 |
|
Isopentenyl-diphosphate Delta-isomeraseUniProtKB:Q46822 | catalyzes Additional IPP/DMAPP interconversion. IspH already produces both products; this is not an obligatory DMAPP-forming step. Left-to-right is the source-selected orientation, not a claim of irreversibility. | Idi interconversion of IPP to DMAPPRHEA:23285 |
|
IspG reduction to HMBPP (flavodoxin reaction family)RHEA:43606 | precedes Native pathway ordering projected to the reviewed reaction mappings. | IspH HMBPP reduction to IPP (chemical-side projection)RHEA:24490 |
|
IspG reduction to HMBPP (flavodoxin reaction family)RHEA:43606 | precedes Native pathway ordering projected to the reviewed reaction mappings. | IspH HMBPP reduction to DMAPP (chemical-side projection)RHEA:24827 |
|
IspF formation of methylerythritol cyclic diphosphateRHEA:23865 | precedes Native pathway ordering projected to the reviewed reaction mappings. | IspG reduction to HMBPP (flavodoxin reaction family)RHEA:43606 |
|
Dxr rearrangement and reduction to MEPRHEA:13719 | precedes Native pathway ordering projected to the reviewed reaction mappings. | IspD cytidylylation of MEPRHEA:13430 |
|
Dxs condensation to 1-deoxy-D-xylulose 5-phosphateRHEA:12606 | precedes Native pathway ordering projected to the reviewed reaction mappings. | Dxr rearrangement and reduction to MEPRHEA:13719 |
|
IspD cytidylylation of MEPRHEA:13430 | precedes Native pathway ordering projected to the reviewed reaction mappings. | IspE phosphorylation of CDP-MERHEA:18438 |
|
IspE phosphorylation of CDP-MERHEA:18438 | precedes Native pathway ordering projected to the reviewed reaction mappings. | IspF formation of methylerythritol cyclic diphosphateRHEA:23865 |
|
IspH HMBPP reduction to IPP (chemical-side projection)RHEA:24490 | precedes Native ordering places optional Idi after the IPP-forming IspH branch; the separate IspH DMAPP-producing branch is retained and does not require Idi. | Idi interconversion of IPP to DMAPPRHEA:23285 |
|
1-deoxy-D-xylulose-5-phosphate synthaseUniProtKB:P77488 | has_cofactor Binds 1 Mg(2+) ion per subunit. | Mg(2+)CHEBI:18420 |
|
1-deoxy-D-xylulose-5-phosphate synthaseUniProtKB:P77488 | has_cofactor Binds 1 thiamine pyrophosphate per subunit. | thiamine diphosphateCHEBI:58937 |
|
1-deoxy-D-xylulose 5-phosphate reductoisomeraseUniProtKB:P45568 | has_cofactor Divalent cation. Prefers Mg(2+), Mn(2+) or Co(2+). These listed metal possibilities do not assert that all three metals are simultaneously required. | Mg(2+)CHEBI:18420 |
|
1-deoxy-D-xylulose 5-phosphate reductoisomeraseUniProtKB:P45568 | has_cofactor Divalent cation. Prefers Mg(2+), Mn(2+) or Co(2+). These listed metal possibilities do not assert that all three metals are simultaneously required. | Mn(2+)CHEBI:29035 |
|
1-deoxy-D-xylulose 5-phosphate reductoisomeraseUniProtKB:P45568 | has_cofactor Divalent cation. Prefers Mg(2+), Mn(2+) or Co(2+). These listed metal possibilities do not assert that all three metals are simultaneously required. | Co(2+)CHEBI:48828 |
|
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferaseUniProtKB:Q46893 | has_cofactor These listed metal possibilities do not assert that all three metals are simultaneously required. The source field supplies no evidence code; no direct experimental claim is inferred. | Mg(2+)CHEBI:18420 |
|
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferaseUniProtKB:Q46893 | has_cofactor These listed metal possibilities do not assert that all three metals are simultaneously required. The source field supplies no evidence code; no direct experimental claim is inferred. | Mn(2+)CHEBI:29035 |
|
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferaseUniProtKB:Q46893 | has_cofactor These listed metal possibilities do not assert that all three metals are simultaneously required. The source field supplies no evidence code; no direct experimental claim is inferred. | Co(2+)CHEBI:48828 |
|
2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthaseUniProtKB:P62617 | has_cofactor Binds 1 divalent metal cation per subunit. | a divalent metal cationCHEBI:60240 |
|
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin)UniProtKB:P62620 | has_cofactor Binds 1 [4Fe-4S] cluster. | [4Fe-4S] clusterCHEBI:49883 |
|
4-hydroxy-3-methylbut-2-enyl diphosphate reductaseUniProtKB:P62623 | has_cofactor Was shown to bind 1 [3Fe-4S] cluster per subunit (PubMed:15469281, PubMed:19569147, PubMed:20080550). However, it initially contains a [4Fe-4S] cluster which easily degrades into a [3Fe-4S] form in the presence of oxygen (PubMed:12706830, PubMed:20080550, PubMed:22137895, PubMed:22687151). | [4Fe-4S] clusterCHEBI:49883 |
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Isopentenyl-diphosphate Delta-isomeraseUniProtKB:Q46822 | has_cofactor Binds 1 Mg(2+) ion per subunit. The magnesium ion binds only when substrate is bound. | Mg(2+)CHEBI:18420 |
|
Isopentenyl-diphosphate Delta-isomeraseUniProtKB:Q46822 | has_cofactor Binds 1 Mn(2+) ion per subunit. | Mn(2+)CHEBI:29035 |
|
Isopentenyl-diphosphate Delta-isomeraseUniProtKB:Q46822 | located_in Contextual localization of Idi only; does not establish localization or exclusivity for other pathway proteins. | cytoplasmGO:0005737 |
|
References
MetaCyc:NONMEVIPP-PWYMetaCyc methylerythritol phosphate pathway I, native pathway definition (source version: MetaCyc 22.5; retrieved 2026-10-10)RHEA:12606Rhea 12606: source-oriented reaction definition (source version: 142 (2026-09-02); exact input is the complete official rhea.rdf.gz archive)RHEA:13719Rhea 13719: source-oriented reaction definition (source version: 142 (2026-09-02); exact input is the complete official rhea.rdf.gz archive)RHEA:13430Rhea 13430: source-oriented reaction definition (source version: 142 (2026-09-02); exact input is the complete official rhea.rdf.gz archive)RHEA:18438Rhea 18438: source-oriented reaction definition (source version: 142 (2026-09-02); exact input is the complete official rhea.rdf.gz archive)RHEA:23865Rhea 23865: source-oriented reaction definition (source version: 142 (2026-09-02); exact input is the complete official rhea.rdf.gz archive)RHEA:43606Rhea 43606: source-oriented reaction definition (source version: 142 (2026-09-02); exact input is the complete official rhea.rdf.gz archive)RHEA:24490Rhea 24490: source-oriented reaction definition (source version: 142 (2026-09-02); exact input is the complete official rhea.rdf.gz archive)RHEA:24827Rhea 24827: source-oriented reaction definition (source version: 142 (2026-09-02); exact input is the complete official rhea.rdf.gz archive)RHEA:23285Rhea 23285: source-oriented reaction definition (source version: 142 (2026-09-02); exact input is the complete official rhea.rdf.gz archive)UniProtKB:P77488UniProtKB P77488: Escherichia coli K-12 enzyme annotation (source version: retrieved 2026-10-10; digest scope is the complete eight-entry batch JSON)UniProtKB:P45568UniProtKB P45568: Escherichia coli K-12 enzyme annotation (source version: retrieved 2026-10-10; digest scope is the complete eight-entry batch JSON)UniProtKB:Q46893UniProtKB Q46893: Escherichia coli K-12 enzyme annotation (source version: retrieved 2026-10-10; digest scope is the complete eight-entry batch JSON)UniProtKB:P62615UniProtKB P62615: Escherichia coli K-12 enzyme annotation (source version: retrieved 2026-10-10; digest scope is the complete eight-entry batch JSON)UniProtKB:P62617UniProtKB P62617: Escherichia coli K-12 enzyme annotation (source version: retrieved 2026-10-10; digest scope is the complete eight-entry batch JSON)UniProtKB:P62620UniProtKB P62620: Escherichia coli K-12 enzyme annotation (source version: retrieved 2026-10-10; digest scope is the complete eight-entry batch JSON)UniProtKB:P62623UniProtKB P62623: Escherichia coli K-12 enzyme annotation (source version: retrieved 2026-10-10; digest scope is the complete eight-entry batch JSON)UniProtKB:Q46822UniProtKB Q46822: Escherichia coli K-12 enzyme annotation (source version: retrieved 2026-10-10; digest scope is the complete eight-entry batch JSON)PMID:11818558Studies on the nonmevalonate terpene biosynthetic pathway: metabolic role of IspH (LytB) protein. — DOI:10.1073/pnas.032658999 (source version: abstract inspected 2026-10-10; Europe PMC MED core JSON)PMID:12571359The deoxyxylulose phosphate pathway of isoprenoid biosynthesis: studies on the mechanisms of the reactions catalyzed by IspG and IspH protein. — DOI:10.1073/pnas.0337742100 (source version: abstract inspected 2026-10-10; Europe PMC MED core JSON)
Curation history
- claude-code
- CREATE — Add the E. coli K-12 MEP I pathway with both IspH product branches
Created MetaCyc NONMEVIPP-PWY with nine reactions, thirty-five participants and sixty-eight edges from native MetaCyc membership/order, Rhea chemistry, UniProt catalytic/cofactor assertions and inspected primary experiments. Retained both IspH products, Idi interconversion, alternative cofactors, evidence grades and six unresolved carrier-state omissions. Corrected Rhea source coefficient extraction during adversarial review. Shared authority snapshots, generated pages, full gates and independent structured review accompany this addition.
- CREATE — Add the E. coli K-12 MEP I pathway with both IspH product branches