MEP isoprenoid precursor biosynthesis

The methylerythritol phosphate (MEP/DOXP) route converts pyruvate and glyceraldehyde 3-phosphate through seven reactions into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). DXS forms the shared branch-point metabolite DXP, Dxr commits DXP to the MEP route, IspD-IspG build HMBPP, and IspH produces the two universal five-carbon isoprenoid precursors. DXP use in thiamine or pyridoxal-phosphate biosynthesis and downstream prenyl-diphosphate elongation are outside this module.

MODULE:mep_isoprenoid_precursor_biosynthesisDRAFTMetabolic Pathwaymodules/mep_isoprenoid_precursor_biosynthesis.yaml
isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathwayGO:0019288 dimethylallyl diphosphate biosynthetic processGO:0050992
GO:0019288
isopentenyl diphosphate biosynthetic process, methylerythritol phosphate pathway
GO:0019288 captures IPP production through the MEP route represented by the seven ordered reactions in this module.
GO:0050992
dimethylallyl diphosphate biosynthetic process
The terminal IspH reaction also produces DMAPP, the second universal five-carbon isoprenoid precursor.
KEGG:M00096
C5 isoprenoid biosynthesis, non-mevalonate pathway
KEGG independently defines the same seven ordered MEP reactions. The terminal IspH reaction directly produces both IPP and DMAPP, so this pathway does not require IDI as an eighth step.
PMID:41700894
Harnessing evolution: leveraging bacterial isoprenoid pathway diversity toward improved bioengineering strategies.
2026 review of bacterial isoprenoid pathway diversity used to audit the module. It confirms the seven-step MEP route with direct IPP/DMAPP output by IspH, and it identifies two unrelated Dxr forms. The second (Dxr-II/DRL) was missing from the earlier module version.
IspH (also referred to as LytB) then converts HMBDP to IDP and DMADP at a ratio favoring IDP, although this ratio is variable based on the enzyme of study (34).
PMID:20660776
A new family of enzymes catalyzing the first committed step of the methylerythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in bacteria.
Primary identification of DRL, a DXR-like oxidoreductase class that catalyzes the Dxr reaction in Brucella abortus and other bacteria lacking canonical Dxr.
These results reveal the existence of a novel class of oxidoreductases catalyzing the conversion of DXP into MEP in prokaryotic cells,
file:modules/mep_isoprenoid_precursor_biosynthesis-deep-research-openscientist.md
OpenScientist MEP isoprenoid precursor biosynthesis module research
Module-level research supports the ordered seven-reaction boundary, Dxr as the first committed step, direct formation of IPP and DMAPP by IspH, and flavodoxin- versus ferredoxin-coupled IspG implementations. Manual assessment excludes regulation, metabolite signaling, detailed Fe-S mechanism, and downstream prenyl metabolism from the reusable core.

This reusable module models the seven-reaction route found in bacteria and plastids. Representative proteins orient each family without restricting the module to those organisms. The IspG step explicitly represents flavodoxin- and ferredoxin-coupled implementations. Prenyl-diphosphate elongation, DXP-dependent vitamin branches, and IPP/DMAPP pool balancing by IDI are outside the boundary. After the 2026 review PMID:41700894, the Dxr step was split into canonical Dxr (Dxr-I) and the unrelated DXR-like DRL class (Dxr-II; PMID:20660776). The review's other variation points are left out of the core: type I vs type II IDI (IDI is outside the boundary), and suppressor mutations that bypass dxs/dxr loss, which are not defined pathway steps.

12Nodes
7Parts
2Variant Sets
4Variants
9Annotons
6Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • mep_isoprenoid_precursor_biosynthesis-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

7 gene-function check(s) reflected in core functions · 0 conflict(s) · 18 evidence or coverage gap(s) (25 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
dxs_activity Dxs (Pseudomonas putida KT2440)
UniProtKB:Q88QG7
Family Representative 		1-deoxy-D-xylulose-5-phosphate synthase activity
GO:0008661 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dxs_activity Dxs (Escherichia coli K-12)
UniProtKB:P77488
Family Representative 		1-deoxy-D-xylulose-5-phosphate synthase activity
GO:0008661 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
dxr_activity Dxr (Pseudomonas putida KT2440)
UniProtKB:Q88MH4
Family Representative 		1-deoxy-D-xylulose-5-phosphate reductoisomerase activity
GO:0030604 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dxr_activity Dxr (Escherichia coli K-12)
UniProtKB:P45568
Family Representative 		1-deoxy-D-xylulose-5-phosphate reductoisomerase activity
GO:0030604 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
drl_activity DRL / BAB2_0264 (Brucella abortus 2308)
UniProtKB:Q2YIM3
Family Representative 		1-deoxy-D-xylulose-5-phosphate reductoisomerase activity
GO:0030604 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ispd_activity IspD (Pseudomonas putida KT2440)
UniProtKB:Q88MF7
Family Representative 		2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activity
GO:0050518 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ispd_activity IspD (Escherichia coli K-12)
UniProtKB:Q46893
Family Representative 		2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activity
GO:0050518 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ispe_activity IspE (Pseudomonas putida KT2440)
UniProtKB:Q88PX5
Family Representative 		4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase activity
GO:0050515 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ispe_activity IspE (Escherichia coli K-12)
UniProtKB:P62615
Family Representative 		4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase activity
GO:0050515 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ispf_activity IspF (Pseudomonas putida KT2440)
UniProtKB:Q88MF3
Family Representative 		2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity
GO:0008685 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ispf_activity IspF (Escherichia coli K-12)
UniProtKB:P62617
Family Representative 		2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity
GO:0008685 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
flavodoxin_ispg_activity IspG (Pseudomonas putida KT2440)
UniProtKB:Q88PJ7
Family Representative 		4-hydroxy-3-methylbut-2-enyl-diphosphate synthase activity (flavodoxin)
GO:0141197 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
flavodoxin_ispg_activity IspG (Escherichia coli K-12)
UniProtKB:P62620
Family Representative 		4-hydroxy-3-methylbut-2-enyl-diphosphate synthase activity (flavodoxin)
GO:0141197 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ferredoxin_ispg_activity IspG (Synechococcus sp. CC9605)
UniProtKB:Q3AK30
Family Representative 		4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase activity (ferredoxin)
GO:0046429 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
isph_activity IspH (Pseudomonas putida KT2440)
UniProtKB:Q88Q89
Family Representative 		4-hydroxy-3-methylbut-2-enyl diphosphate reductase activity
GO:0051745 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
isph_activity IspH (Escherichia coli K-12)
UniProtKB:P62623
Family Representative 		4-hydroxy-3-methylbut-2-enyl diphosphate reductase activity
GO:0051745 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
dxs_activity DXP synthase family
PANTHER:PTHR43322:SF5
Family 		1-deoxy-D-xylulose-5-phosphate synthase activity
GO:0008661 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43322:SF5.
dxr_activity DXP reductoisomerase family
PANTHER:PTHR30525:SF0
Family 		1-deoxy-D-xylulose-5-phosphate reductoisomerase activity
GO:0030604 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR30525:SF0.
drl_activity DRL (DXR-like) oxidoreductase family
Family 		1-deoxy-D-xylulose-5-phosphate reductoisomerase activity
GO:0030604 		Family Id Missing
The family has no identifier linking it to a curated family review.
ispd_activity IspD MEP cytidylyltransferase family
PANTHER:PTHR32125:SF4
Family 		2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activity
GO:0050518 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR32125:SF4.
ispe_activity IspE CDP-ME kinase family
PANTHER:PTHR43527:SF2
Family 		4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase activity
GO:0050515 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43527:SF2.
ispf_activity IspF ME-CPP synthase family
PANTHER:PTHR43181:SF1
Family 		2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity
GO:0008685 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43181:SF1.
flavodoxin_ispg_activity IspG HMBPP synthase family
PANTHER:PTHR30454
Family 		4-hydroxy-3-methylbut-2-enyl-diphosphate synthase activity (flavodoxin)
GO:0141197 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR30454.
ferredoxin_ispg_activity IspG HMBPP synthase family
PANTHER:PTHR30454
Family 		4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase activity (ferredoxin)
GO:0046429 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR30454.
isph_activity IspH HMBPP reductase family
PANTHER:PTHR30426:SF0
Family 		4-hydroxy-3-methylbut-2-enyl diphosphate reductase activity
GO:0051745 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR30426:SF0.

Gene-review completeness (7/16 grounded genes reviewed)

7 complete review(s) · 7 with deep research · 9 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
dxr Q88MH4 ✓ ✓ ✓
dxs Q88QG7 ✓ ✓ ✓
ispD Q88MF7 ✓ ✓ ✓
ispE Q88PX5 ✓ ✓ ✓
ispF Q88MF3 ✓ ✓ ✓
ispG Q88PJ7 ✓ ✓ ✓
ispH Q88Q89 ✓ ✓ ✓
Dxr (Escherichia coli K-12) P45568 ✗ — —
IspE (Escherichia coli K-12) P62615 ✗ — —
IspF (Escherichia coli K-12) P62617 ✗ — —
IspG (Escherichia coli K-12) P62620 ✗ — —
IspH (Escherichia coli K-12) P62623 ✗ — —
Dxs (Escherichia coli K-12) P77488 ✗ — —
DRL / BAB2_0264 (Brucella abortus 2308) Q2YIM3 ✗ — —
IspG (Synechococcus sp. CC9605) Q3AK30 ✗ — —
IspD (Escherichia coli K-12) Q46893 ✗ — —

Details

MEP isoprenoid precursor biosynthesisMetabolic Pathwaymep_isoprenoid_precursor_biosynthesis
isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathwayGO:0019288 dimethylallyl diphosphate biosynthetic processGO:0050992

Connections

dxs_dxp_formation -> dxr_mep_formation Provides Input For
DXS supplies DXP to the committed MEP reaction.
Dxr supplies MEP to IspD.
IspD supplies CDP-ME to IspE.
IspE supplies CDP-ME 2-phosphate to IspF.
IspF supplies ME-CPP to IspG.
IspG supplies HMBPP to the terminal IspH reaction.
Part 1: DXP formation from pyruvate and glyceraldehyde 3-phosphate
DXS-dependent DXP formationReactiondxs_dxp_formation

DXS performs a thiamine-diphosphate-dependent condensation that supplies DXP to the MEP route and to vitamin-biosynthesis branches.

Annotons

DXP synthase activity
dxs_activity
Participant: Family: DXP synthase family
Family:
DXP synthase familyPANTHER:PTHR43322:SF5 The official SF5 label is chloroplast-biased, but the local member index places both reviewed bacterial exemplars in this exact subfamily. The label is retained verbatim and does not impose chloroplast localization on the reusable role.
Representative Members: Dxs (Pseudomonas putida KT2440)UniProtKB:Q88QG7 Dxs (Escherichia coli K-12)UniProtKB:P77488
Required Function:
1-deoxy-D-xylulose-5-phosphate synthase activityGO:0008661

Function

1-deoxy-D-xylulose-5-phosphate synthase activityGO:0008661
Substrates: pyruvate D-glyceraldehyde 3-phosphate
Products: 1-deoxy-D-xylulose 5-phosphate carbon dioxide

Produces DXP at the entry to the route without implying that DXS is committed exclusively to isoprenoid precursor biosynthesis.

Part 2: Commitment of DXP to MEP
DXP reductoisomerase-dependent MEP formationReactiondxr_mep_formation

Two unrelated enzyme classes catalyze the same NADPH-dependent DXP to MEP reaction. Canonical Dxr (Dxr-I) and the DXR-like DRL class (Dxr-II) share sequence similarity only in the NADPH-binding region, and DRL is scattered sporadically across bacteria (PMID:41700894, PMID:20660776).

Variant set: DXP reductoisomerase enzyme class by enzyme family (One Or More)
Canonical Dxr (Dxr-I)Reactiondxr_type_i_variant

Annotons

DXP reductoisomerase activity
dxr_activity
Participant: Family: DXP reductoisomerase family
Family:
DXP reductoisomerase familyPANTHER:PTHR30525:SF0 The official SF0 label is chloroplast-biased, while the verified membership includes reviewed bacterial Dxr proteins. The exact label is retained without asserting localization.
Representative Members: Dxr (Pseudomonas putida KT2440)UniProtKB:Q88MH4 Dxr (Escherichia coli K-12)UniProtKB:P45568
Required Function:
1-deoxy-D-xylulose-5-phosphate reductoisomerase activityGO:0030604

Function

1-deoxy-D-xylulose-5-phosphate reductoisomerase activityGO:0030604
Substrates: 1-deoxy-D-xylulose 5-phosphate NADPH
Products: 2-C-methyl-D-erythritol 4-phosphate NADP+

Commits DXP to the MEP isoprenoid precursor route.

DXR-like DRL (Dxr-II)Reactiondrl_type_ii_variant

Annotons

DRL DXP reductoisomerase activity
drl_activity
Participant: Family: DRL (DXR-like) oxidoreductase family
Family:
DRL (DXR-like) oxidoreductase family No PANTHER id is asserted. The Brucella abortus DRL falls in PTHR37850 ("STRU PROTEIN"), but that family also holds proteins with other functions, and no family-level DRL assignment has been established.
Representative Members: DRL / BAB2_0264 (Brucella abortus 2308)UniProtKB:Q2YIM3

Function

1-deoxy-D-xylulose-5-phosphate reductoisomerase activityGO:0030604
Substrates: 1-deoxy-D-xylulose 5-phosphate NADPH
Products: 2-C-methyl-D-erythritol 4-phosphate NADP+

Commits DXP to the MEP route in bacteria that lack canonical Dxr, such as Brucella.

Part 3: CDP-ME formation
IspD-dependent CDP-ME formationReactionispd_cdp_me_formation

Annotons

MEP cytidylyltransferase activity
ispd_activity
Participant: Family: IspD MEP cytidylyltransferase family
Family:
IspD MEP cytidylyltransferase familyPANTHER:PTHR32125:SF4 The official SF4 label is chloroplast-biased, but the exact subfamily contains the reviewed bacterial IspD exemplars. The label is retained verbatim without asserting localization.
Representative Members: IspD (Pseudomonas putida KT2440)UniProtKB:Q88MF7 IspD (Escherichia coli K-12)UniProtKB:Q46893
Required Function:
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activityGO:0050518

Function

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activityGO:0050518
Substrates: 2-C-methyl-D-erythritol 4-phosphate CTP
Products: 4-diphosphocytidyl-2-C-methyl-D-erythritol diphosphate

Converts MEP to the cytidylated intermediate CDP-ME.

Part 4: CDP-ME 2-phosphate formation
IspE-dependent CDP-ME 2-phosphate formationReactionispe_cdp_me2p_formation

Annotons

CDP-ME kinase activity
ispe_activity
Participant: Family: IspE CDP-ME kinase family
Family:
IspE CDP-ME kinase familyPANTHER:PTHR43527:SF2 The official SF2 label is chloroplast-biased, but the exact subfamily contains the reviewed bacterial IspE exemplars. The label is retained verbatim without asserting localization.
Representative Members: IspE (Pseudomonas putida KT2440)UniProtKB:Q88PX5 IspE (Escherichia coli K-12)UniProtKB:P62615
Required Function:
4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase activityGO:0050515

Function

4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase activityGO:0050515
Substrates: 4-diphosphocytidyl-2-C-methyl-D-erythritol ATP
Products: 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate ADP

Phosphorylates CDP-ME to form CDP-ME 2-phosphate.

Part 5: ME-CPP formation
IspF-dependent ME-CPP formationReactionispf_me_cpp_formation

Annotons

ME-CPP synthase activity
ispf_activity
Participant: Family: IspF ME-CPP synthase family
Family:
IspF ME-CPP synthase familyPANTHER:PTHR43181:SF1 The official SF1 label is chloroplast-biased, while the local member index places both reviewed bacterial IspF exemplars in this exact subfamily. The label is retained verbatim without asserting localization.
Representative Members: IspF (Pseudomonas putida KT2440)UniProtKB:Q88MF3 IspF (Escherichia coli K-12)UniProtKB:P62617
Required Function:
2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activityGO:0008685

Function

2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activityGO:0008685
Substrates: 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate
Products: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate CMP

Cyclizes CDP-ME 2-phosphate to form ME-CPP.

Part 6: HMBPP formation
IspG-dependent HMBPP formationReactionispg_hmbpp_formation

IspG reductively converts ME-CPP to HMBPP using a low-potential electron carrier. The carrier-specific activity differs among lineages without changing the pathway intermediate produced.

Variant set: IspG electron-carrier variants by electron carrier (One Or More)
Flavodoxin-coupled IspGReactionflavodoxin_ispg_variant

Annotons

Flavodoxin-coupled HMBPP synthase activity
flavodoxin_ispg_activity
Participant: Family: IspG HMBPP synthase family
Family:
IspG HMBPP synthase familyPANTHER:PTHR30454 The parent family is used because its indexed SF0 is officially labeled ferredoxin/chloroplastic yet contains reviewed flavodoxin-coupled bacterial IspG. Electron-carrier specificity is imposed by the required function and Rhea reaction, not by PANTHER.
Representative Members: IspG (Pseudomonas putida KT2440)UniProtKB:Q88PJ7 IspG (Escherichia coli K-12)UniProtKB:P62620
Required Function:
4-hydroxy-3-methylbut-2-enyl-diphosphate synthase activity (flavodoxin)GO:0141197

Function

4-hydroxy-3-methylbut-2-enyl-diphosphate synthase activity (flavodoxin)GO:0141197
Substrates: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate reduced flavodoxin
Products: 4-hydroxy-3-methylbut-2-enyl diphosphate oxidized flavodoxin

Reductively converts ME-CPP to HMBPP using flavodoxin.

Ferredoxin-coupled IspGReactionferredoxin_ispg_variant

Annotons

Ferredoxin-coupled HMBPP synthase activity
ferredoxin_ispg_activity
Participant: Family: IspG HMBPP synthase family
Family:
IspG HMBPP synthase familyPANTHER:PTHR30454 The parent family is used because PANTHER SF0 does not cleanly separate electron-carrier implementations. Ferredoxin specificity is grounded by the required function, Rhea 26119, and reviewed Q3AK30 exemplar.
Representative Members: IspG (Synechococcus sp. CC9605)UniProtKB:Q3AK30
Required Function:
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase activity (ferredoxin)GO:0046429

Function

4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase activity (ferredoxin)GO:0046429
Substrates: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate reduced [2Fe-2S] ferredoxin
Products: 4-hydroxy-3-methylbut-2-enyl diphosphate oxidized [2Fe-2S] ferredoxin

Reductively converts ME-CPP to HMBPP using ferredoxin.

Part 7: IPP and DMAPP formation
IspH-dependent IPP and DMAPP formationReactionisph_ipp_dmapp_formation

Annotons

HMBPP reductase activity
isph_activity
Participant: Family: IspH HMBPP reductase family
Family:
IspH HMBPP reductase familyPANTHER:PTHR30426:SF0
Representative Members: IspH (Pseudomonas putida KT2440)UniProtKB:Q88Q89 IspH (Escherichia coli K-12)UniProtKB:P62623
Required Function:
4-hydroxy-3-methylbut-2-enyl diphosphate reductase activityGO:0051745

Function

4-hydroxy-3-methylbut-2-enyl diphosphate reductase activityGO:0051745
Substrates: 4-hydroxy-3-methylbut-2-enyl diphosphate reduced ferredoxin
Products: isopentenyl diphosphate dimethylallyl diphosphate oxidized ferredoxin

Produces the IPP and DMAPP outputs of the pathway.