Aerobic nicotinate degradation through 2,5-dihydroxypyridine

A reusable six-reaction bacterial pathway that converts nicotinate to fumarate through 6-hydroxynicotinate, 2,5-dihydroxypyridine, N-formylmaleamate, maleamate, and maleate. NicAB performs the initial cytochrome-linked hydroxylation, NicC performs an oxygen- and NADH-dependent oxidative decarboxylation, NicX opens the pyridine ring, NicD removes the formyl group, NicF releases the amide nitrogen, and MaiA isomerizes maleate to fumarate.

MODULE:aerobic_nicotinate_degradationDRAFTCONCRETEMetabolic Pathwaymodules/aerobic_nicotinate_degradation.yaml
nicotinate catabolic processGO:1901848
GO:1901848
nicotinate catabolic process
GO:1901848 captures degradation of nicotinate represented by this ordered route.
UniPathway:UPA01010
nicotinate degradation
The PSEPK UniPathway membership groups the characterized nic genes for aerobic nicotinate degradation.
PMID:18678916
Deciphering the genetic determinants for aerobic nicotinic acid degradation: the nic cluster from Pseudomonas putida KT2440.
This study experimentally characterized the P. putida KT2440 nicotinate degradation gene cluster and the pathway intermediates.
file:PSEPK/nicA/nicA-ai-review.yaml
PSEPK nicA gene review
Q88FX9 is the iron-sulfur small subunit of the NicAB nicotinate dehydrogenase.
file:PSEPK/nicB/nicB-ai-review.yaml
PSEPK nicB gene review
Q88FX8 is the molybdenum/heme-containing large subunit of NicAB.

The pathway is species-neutral but grounded by the experimentally characterized Pseudomonas putida KT2440 system. The broad GO molecular function available for NicAB, NicD, and NicF does not encode their precise substrate specificity, so their exact EC numbers and Rhea reactions define the leaf chemistry. NicR and NicS regulate expression but are not required catalytic parts. Nicotinate uptake, cofactor assembly, cytochrome oxidase, and downstream fumarate metabolism are outside the boundary.

7Nodes
6Parts
0Variant Sets
0Variants
6Annotons
5Connections

Derived QC

Recommended-field compliance

53.8% recommended fields populated
  • module.knowledge_gaps[0] · status (0/1)
  • module.knowledge_gaps[0] · provenance (0/1)
  • module.knowledge_gaps[1] · status (0/1)
  • module.knowledge_gaps[1] · provenance (0/1)
  • module.knowledge_gaps[2] · status (0/1)
  • module.knowledge_gaps[2] · provenance (0/1)

Module deep research

✗ none found

No MODULE:aerobic_nicotinate_degradation deep-research report alongside the module YAML.

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 (7/7 grounded genes reviewed)

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

Gene Review Complete Deep research
maiA Q88FY4 ✓ ✓ ✓
nicA Q88FX9 ✓ ✓ ✓
nicB Q88FX8 ✓ ✓ ✓
nicC Q88FY2 ✓ ✓ ✓
nicD Q88FY3 ✓ ✓ ✓
nicF Q88FY5 ✓ ✓ ✓
nicX Q88FY1 ✓ ✓ ✓

Details

Context
bacteriaNCBITaxon:2
Aerobic nicotinate degradation through 2,5-dihydroxypyridineMetabolic Pathwayaerobic_nicotinate_degradation
nicotinate catabolic processGO:1901848
Context
bacteriaNCBITaxon:2

Connections

NicAB produces the 6-hydroxynicotinate consumed by NicC.
NicC produces the 2,5-dihydroxypyridine consumed by NicX.
nicx_ring_cleavage -> nicd_deformylation Provides Input For
NicX produces the N-formylmaleamate consumed by NicD.
NicD produces the maleamate consumed by NicF.
NicF produces the maleate consumed by MaiA.
Part 1: nicotinate hydroxylation
NicAB-dependent 6-hydroxynicotinate formationReactionnicab_nicotinate_hydroxylation

Annotons

NicAB nicotinate dehydrogenase activity
nicab_activity
Participant: Protein Complex: NicAB nicotinate dehydrogenase complex
Protein Complex:
NicAB nicotinate dehydrogenase complex
Active units:
NicA iron-sulfur subunit
Participant: Family: NicA nicotinate dehydrogenase small-subunit family
Family:
NicA nicotinate dehydrogenase small-subunit familyPANTHER:PTHR44379:SF6
Representative Members: NicA (Pseudomonas putida KT2440)UniProtKB:Q88FX9
Role: Relays electrons through two [2Fe-2S] clusters.
NicB catalytic and cytochrome electron-transfer subunit
Participant: Family: NicB nicotinate dehydrogenase large-subunit family
Family:
NicB nicotinate dehydrogenase large-subunit familyInterPro:IPR052516
Representative Members: NicB (Pseudomonas putida KT2440)UniProtKB:Q88FX8
Role: Binds the molybdenum cofactor and heme centers required for nicotinate hydroxylation and cytochrome reduction.

Function

oxidoreductase activity, acting on CH or CH2 groupsGO:0016725
Substrates: nicotinate water oxidized cytochrome
Products: 6-hydroxynicotinate reduced cytochrome proton

Processes

nicotinate catabolic processGO:1901848

Introduces the first hydroxyl group into nicotinate.

Part 2: oxidative decarboxylation of 6-hydroxynicotinate
NicC-dependent 2,5-dihydroxypyridine formationReactionnicc_dihydroxypyridine_formation

Annotons

NicC 6-hydroxynicotinate 3-monooxygenase activity
nicc_activity
Participant: Family: NicC monooxygenase family
Family:
NicC monooxygenase familyPANTHER:PTHR13789:SF309
Representative Members: NicC (Pseudomonas putida KT2440)UniProtKB:Q88FY2

Function

6-hydroxynicotinate 3-monooxygenase activityGO:0043731
Substrates: 6-hydroxynicotinate NADH oxygen proton
Products: 2,5-dihydroxypyridine carbon dioxide NAD+ water

Processes

nicotinate catabolic processGO:1901848

Produces the dioxygenase substrate 2,5-dihydroxypyridine.

Part 3: pyridine-ring cleavage
NicX-dependent N-formylmaleamate formationReactionnicx_ring_cleavage

Annotons

NicX 2,5-dihydroxypyridine dioxygenase activity
nicx_activity
Participant: Family: NicX dioxygenase family
Family:
NicX dioxygenase familyInterPro:IPR058739
Representative Members: NicX (Pseudomonas putida KT2440)UniProtKB:Q88FY1

Function

2,5-dihydroxypyridine 5,6-dioxygenase activityGO:0047075
Substrates: 2,5-dihydroxypyridine oxygen
Products: N-formylmaleamate proton

Processes

nicotinate catabolic processGO:1901848

Opens the aromatic pyridine ring.

Part 4: N-formylmaleamate deformylation
NicD-dependent maleamate formationReactionnicd_deformylation

Annotons

NicD N-formylmaleamate deformylase activity
nicd_activity
Participant: Family: NicD deformylase family
Family:
NicD deformylase familyPANTHER:PTHR43798:SF33
Representative Members: NicD (Pseudomonas putida KT2440)UniProtKB:Q88FY3

Function

hydrolase activity, acting on carbon-nitrogen bonds in linear amidesGO:0016811
Substrates: N-formylmaleamate water
Products: maleamate formate proton

Processes

nicotinate catabolic processGO:1901848

Removes the formyl group after ring opening.

Part 5: maleamate deamidation
NicF-dependent maleate formationReactionnicf_maleate_formation

Annotons

NicF maleamate amidohydrolase activity
nicf_activity
Participant: Family: NicF maleamate amidohydrolase family
Family:
NicF maleamate amidohydrolase familyPANTHER:PTHR43540:SF1
Representative Members: NicF (Pseudomonas putida KT2440)UniProtKB:Q88FY5

Function

hydrolase activity, acting on carbon-nitrogen bonds in linear amidesGO:0016811
Substrates: maleamate water
Products: maleate ammonium

Processes

nicotinate catabolic processGO:1901848

Releases the pathway nitrogen and forms maleate.

Part 6: maleate isomerization
MaiA-dependent fumarate formationReactionmaia_fumarate_formation

Annotons

MaiA maleate isomerase activity
maia_activity
Participant: Family: MaiA maleate isomerase family
Family:
MaiA maleate isomerase familyInterPro:IPR028615
Representative Members: MaiA (Pseudomonas putida KT2440)UniProtKB:Q88FY4

Function

maleate isomerase activityGO:0050076
Substrates: maleate
Products: fumarate

Processes

nicotinate catabolic processGO:1901848

Produces fumarate for entry into central metabolism.