De novo inosine monophosphate biosynthesis

A reusable pathway that assembles the purine ring on 5-phosphoribosyl diphosphate (PRPP) to form inosine monophosphate (IMP). The module represents ten ordered reaction positions and separates reaction roles from lineage-specific protein fusions. It includes alternative folate-dependent PurN and ATP/formate-dependent PurT routes for GAR formylation, and alternative two-enzyme and direct routes for AIR carboxylation. IMP-to-AMP and IMP-to-GMP branches are outside the module, although PurB also has a second physiological role in AMP synthesis.

MODULE:de_novo_purine_synthesisDRAFTMetabolic Pathwaymodules/de_novo_purine_synthesis.yaml

'de novo' IMP biosynthetic processGO:0006189

GO:0006189

'de novo' IMP biosynthetic process

GO:0006189 defines the pathway from PRPP through purine-ring assembly to IMP.

file:modules/de_novo_purine_synthesis-deep-research-openscientist.md

OpenScientist research for de novo IMP biosynthesis

The generic pathway review supports the ordered reaction boundary, alternative GAR-formylation chemistry, AIR-carboxylation variants, and lineage-specific fusion architectures.

PMID:8501063

Evidence for a novel glycinamide ribonucleotide transformylase in Escherichia coli

Genetic analysis establishes PurN and PurT as alternative GAR transformylases at the same de novo purine-biosynthesis position.

PMID:10574791

Crystal structure of Escherichia coli PurE, an unusual mutase in the purine biosynthetic pathway

Structural and biochemical evidence distinguishes the bacterial PurK/PurE N5-CAIR route from direct AIR carboxylation.

file:human/PPAT/PPAT-ai-review.yaml

Human PPAT gene review

Q06203 provides a eukaryotic exemplar for the committed first reaction.

file:human/GART/GART-ai-review.yaml

Human GART gene review

P22102 exemplifies fusion of the PurD-, PurN-, and PurM-like reaction roles.

file:human/PFAS/PFAS-ai-review.yaml

Human PFAS gene review

O15067 provides a eukaryotic exemplar for FGAM synthase activity.

file:human/PAICS/PAICS-ai-review.yaml

Human PAICS gene review

P22234 exemplifies fusion of direct AIR carboxylase and SAICAR synthetase roles.

file:human/ADSL/ADSL-ai-review.yaml

Human ADSL gene review

P30566 provides a eukaryotic exemplar for the two physiological PurB lyase activities.

file:human/ATIC/ATIC-ai-review.yaml

Human ATIC gene review

P31939 exemplifies fusion of the final AICAR transformylase and IMP cyclohydrolase roles.

file:PSEPK/purF/purF-ai-review.yaml

PSEPK purF gene review

Q88LD5 supplies the committed amidophosphoribosyltransferase step.

file:PSEPK/purD/purD-ai-review.yaml

PSEPK purD gene review

Q88DK2 supplies phosphoribosylamine--glycine ligase activity.

file:PSEPK/purN/purN-ai-review.yaml

PSEPK purN gene review

Q88MB0 supplies the folate-dependent GAR transformylase route.

file:PSEPK/purT/purT-ai-review.yaml

PSEPK purT gene review

Q88MW1 supplies the ATP/formate-dependent GAR transformylase route.

file:PSEPK/purL/purL-ai-review.yaml

PSEPK purL gene review

Q88P16 supplies large-type FGAM synthase activity.

file:PSEPK/purM/purM-ai-review.yaml

PSEPK purM gene review

Q88MA9 supplies AIR synthetase activity.

file:PSEPK/purK/purK-ai-review.yaml

PSEPK purK gene review

Q88C48 supplies N5-CAIR synthetase activity.

file:PSEPK/purE/purE-ai-review.yaml

PSEPK purE gene review

Q88C47 supplies N5-CAIR mutase activity.

file:PSEPK/purC/purC-ai-review.yaml

PSEPK purC gene review

Q88NG9 supplies SAICAR synthetase activity.

file:PSEPK/purB/purB-ai-review.yaml

PSEPK purB gene review

Q88FR7 supplies SAICAR lyase activity in this module.

file:PSEPK/purH/purH-ai-review.yaml

PSEPK purH gene review

Q88DK3 supplies the final AICAR transformylase and IMP cyclohydrolase reactions.

17Nodes

12Parts

2Variant Sets

4Variants

13Annotons

10Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

de_novo_purine_synthesis-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.

Gene-review completeness (17/27 grounded genes reviewed)

17 complete review(s) · 4 with deep research · 10 missing review · 13 reviewed but lacking deep research

Gene	Review	Complete	Deep research
ADSL P30566	✓	✓	✗
ATIC P31939	✓	✓	✗
GART P22102	✓	✓	✗
Escherichia coli PurM P08178	✗	—	—
Escherichia coli PurN P08179	✗	—	—
Escherichia coli PurK P09029	✗	—	—
Escherichia coli PurB P0AB89	✗	—	—
Escherichia coli PurF P0AG16	✗	—	—
Escherichia coli PurE P0AG18	✗	—	—
Escherichia coli PurL P15254	✗	—	—
Escherichia coli PurH P15639	✗	—	—
Escherichia coli PurD P15640	✗	—	—
Escherichia coli PurT P33221	✗	—	—
PAICS P22234	✓	✓	✗
PFAS O15067	✓	✓	✗
PPAT Q06203	✓	✓	✗
purB Q88FR7	✓	✓	✗
purC Q88NG9	✓	✓	✓
purD Q88DK2	✓	✓	✓
purE Q88C47	✓	✓	✗
purF Q88LD5	✓	✓	✓
purH Q88DK3	✓	✓	✗
purK Q88C48	✓	✓	✗
purL Q88P16	✓	✓	✗
purM Q88MA9	✓	✓	✗
purN Q88MB0	✓	✓	✓
purT Q88MW1	✓	✓	✗

Tree

De novo inosine monophosphate biosynthesisMetabolic Pathwayde_novo_purine_synthesis

Parts
1. 1. committed phosphoribosylamine formation
2. AmidophosphoribosyltransferaseReactionpurF_step
  
  Annotons
  - Glutamine PRPP amidotransferase Family: PurF amidophosphoribosyltransferases
3. 2. glycinamide ribonucleotide formation
4. Phosphoribosylamine--glycine ligaseReactionpurD_step
  
  Annotons
  - GAR synthetase Family: PurD phosphoribosylamine--glycine ligases
5. 3. GAR formylation
6. Alternative GAR transformylation routesReactiongar_transformylation_step
  
  Variants
  1. GAR one-carbon donor route by one-carbon donor and energy coupling (One Or More)
    
    Folate-dependent PurN routeReactionpurN_folate_route
    
    Annotons
    
    Folate-dependent GAR transformylase Family: PurN GAR transformylases
    
    ATP/formate-dependent PurT routeReactionpurT_formate_route
    
    Annotons
    
    Formate-dependent GAR transformylase Family: PurT formate-dependent GAR transformylases
7. 4. formylglycinamidine ribonucleotide formation
8. Phosphoribosylformylglycinamidine synthaseReactionpurL_step
  
  Annotons
  - FGAM synthase Family: large-type PurL FGAM synthases
9. 5. aminoimidazole ribonucleotide formation
10. Phosphoribosylformylglycinamidine cyclo-ligaseReactionpurM_step
  
  Annotons
  - AIR synthetase Family: PurM AIR synthetases
11. 6. aminoimidazole ribonucleotide carboxylation
12. Alternative AIR carboxylation routesMetabolic Pathwayair_carboxylation_step
  
  Variants
  1. AIR-to-CAIR implementation by direct versus N5-CAIR intermediate (Exactly One)
    
    Two-enzyme PurK/PurE routeMetabolic Pathwaytwo_enzyme_n5_cair_route
    
    Parts
    
    1. N5-CAIR formation
    
    N5-CAIR synthetaseReactionpurK_substep
    
    Annotons
    
    ATP-dependent N5-CAIR synthetase Family: PurK N5-CAIR synthetases
    
    2. CAIR rearrangement
    
    N5-CAIR mutaseReactionpurE_substep
    
    Annotons
    
    N5-CAIR mutase Family: PurE N5-CAIR mutases
    
    Direct AIR carboxylase routeReactiondirect_air_carboxylase_route
    
    Annotons
    
    Direct AIR carboxylase Family: direct AIR carboxylases and PAICS-type fusion proteins
13. 7. succinylaminoimidazole carboxamide ribonucleotide formation
14. SAICAR synthetaseReactionpurC_step
  
  Annotons
  - SAICAR synthetase Family: PurC and PAICS SAICAR synthetases
15. 8. aminoimidazole carboxamide ribonucleotide formation
16. SAICAR lyaseReactionpurB_step
  
  Annotons
  - SAICAR lyase Family: PurB adenylosuccinate lyases
17. 9. formylaminoimidazole carboxamide ribonucleotide formation
18. AICAR transformylaseReactionpurH_transformylase_step
  
  Annotons
  - AICAR transformylase Family: PurH and ATIC AICAR transformylases
19. 10. inosine monophosphate formation
20. IMP cyclohydrolaseReactionpurH_cyclohydrolase_step
  
  Annotons
  - IMP cyclohydrolase Family: PurH and ATIC IMP cyclohydrolases

Details

De novo inosine monophosphate biosynthesisMetabolic Pathwayde_novo_purine_synthesis

'de novo' IMP biosynthetic processGO:0006189

Exact UniProt exemplars delimit each reaction role without restricting the module taxonomically. A multidomain protein may satisfy more than one leaf: GART combines PurD-, PurN-, and PurM-like roles, PAICS combines direct AIR carboxylase and SAICAR synthetase roles, and PurH/ATIC commonly combines the final two reactions. Parent PANTHER families containing both standalone enzymes and fusion proteins are selector scaffolds constrained by the leaf molecular function and exemplars. No ancestral PTN node is asserted without verified PAINT IBD evidence.

Connections

purF_step -> purD_step Provides Input For

PurF supplies phosphoribosylamine to PurD.

purD_step -> gar_transformylation_step Provides Input For

PurD supplies GAR to either transformylase route.

gar_transformylation_step -> purL_step Provides Input For

GAR formylation supplies FGAR to PurL.

purL_step -> purM_step Provides Input For

PurL supplies FGAM to PurM.

purM_step -> air_carboxylation_step Provides Input For

PurM supplies AIR to the selected carboxylation route.

air_carboxylation_step -> purC_step Provides Input For

AIR carboxylation supplies CAIR to SAICAR synthetase.

purC_step -> purB_step Provides Input For

PurC supplies SAICAR to PurB.

purB_step -> purH_transformylase_step Provides Input For

PurB supplies AICAR to the penultimate reaction.

purH_transformylase_step -> purH_cyclohydrolase_step Provides Input For

AICAR transformylation supplies FAICAR for ring closure.

Part 1: committed phosphoribosylamine formation

AmidophosphoribosyltransferaseReactionpurF_step

Annotons

Glutamine PRPP amidotransferase

purF_activity

Participant: Family: PurF amidophosphoribosyltransferases

Family:

PurF amidophosphoribosyltransferasesPANTHER:PTHR11907

Representative Members: PSEPK PurFUniProtKB:Q88LD5 Escherichia coli PurFUniProtKB:P0AG16 Human PPATUniProtKB:Q06203

Function

amidophosphoribosyltransferase activityGO:0004044

Substrates: 5-phosphoribosyl diphosphate L-glutamine water

Products: 5-phosphoribosylamine L-glutamate diphosphate

Commits PRPP to de novo purine-ring assembly.

Part 2: glycinamide ribonucleotide formation

Phosphoribosylamine--glycine ligaseReactionpurD_step

Annotons

GAR synthetase

purD_activity

Participant: Family: PurD phosphoribosylamine--glycine ligases

Family:

PurD phosphoribosylamine--glycine ligasesPANTHER:PTHR43472

Representative Members: PSEPK PurDUniProtKB:Q88DK2 Escherichia coli PurDUniProtKB:P15640 Human GARTUniProtKB:P22102

Function

phosphoribosylamine-glycine ligase activityGO:0004637

Substrates: 5-phosphoribosylamine glycine ATP

Products: phosphoribosylglycinamide ADP phosphate

Adds glycine to the growing purine precursor.

Part 3: GAR formylation

Alternative GAR transformylation routesReactiongar_transformylation_step

Variant set: GAR one-carbon donor route by one-carbon donor and energy coupling (One Or More)

Folate-dependent PurN routeReactionpurN_folate_route

Annotons

Folate-dependent GAR transformylase

purN_activity

Participant: Family: PurN GAR transformylases

Family:

PurN GAR transformylasesPANTHER:PTHR43369

Representative Members: PSEPK PurNUniProtKB:Q88MB0 Escherichia coli PurNUniProtKB:P08179 Human GARTUniProtKB:P22102

phosphoribosylformylglycinamidine cyclo-ligase activityGO:0004641

Substrates: phosphoribosylformylglycinamidine ATP

Products: 5-aminoimidazole ribonucleotide ADP phosphate

Cyclizes FGAM to form the first purine-ring intermediate AIR.

Part 6: aminoimidazole ribonucleotide carboxylation

Alternative AIR carboxylation routesMetabolic Pathwayair_carboxylation_step

Variant set: AIR-to-CAIR implementation by direct versus N5-CAIR intermediate (Exactly One)

Two-enzyme PurK/PurE routeMetabolic Pathwaytwo_enzyme_n5_cair_route

Connections

purK_substep -> purE_substep Provides Input For

PurK supplies N5-CAIR to PurE.

Part 1: N5-CAIR formation

N5-CAIR synthetaseReactionpurK_substep

Annotons

ATP-dependent N5-CAIR synthetase

purK_activity

Participant: Family: PurK N5-CAIR synthetases

Family:

PurK N5-CAIR synthetasesPANTHER:PTHR11609

Representative Members: PSEPK PurKUniProtKB:Q88C48 Escherichia coli PurKUniProtKB:P09029

Function

5-(carboxyamino)imidazole ribonucleotide synthase activityGO:0034028

Substrates: 5-aminoimidazole ribonucleotide hydrogencarbonate ATP

Products: N5-carboxyaminoimidazole ribonucleotide ADP phosphate

Part 2: CAIR rearrangement

N5-CAIR mutaseReactionpurE_substep

Annotons

N5-CAIR mutase

purE_activity

Participant: Family: PurE N5-CAIR mutases

Family:

PurE N5-CAIR mutasesPANTHER:PTHR23046

IMP cyclohydrolase activityGO:0003937

Substrates: FAICAR

Products: inosine monophosphate water

Closes the second purine ring to produce IMP.