2-methylcitrate cycle

A reusable propionate-assimilation module that activates propionate to propionyl-CoA, condenses propionyl-CoA with oxaloacetate to form 2-methylcitrate, converts 2-methylcitrate to 2-methylisocitrate through alternative dehydration/isomerization implementations, and cleaves 2-methylisocitrate to succinate and pyruvate. The module distinguishes the direct PrpD route from the two-component AcnD/PrpF route and represents the common aconitase-family hydration step separately.

MODULE:methylcitrate_cycleDRAFTMetabolic Pathwaymodules/methylcitrate_cycle.yaml
propionate catabolic processGO:0019543
GO:0019543
propionate catabolic process
GO:0019543 provides the biological-process scope for catabolism of propionate through propionyl-CoA and the 2-methylcitrate pathway.
file:PSEPK/prpC/prpC-ai-review.yaml
PSEPK prpC gene review
The curated KT2440 review identifies Q88KF5 as the 2-methylcitrate synthase rather than the housekeeping TCA citrate synthase.
file:PSEPK/acnB/acnB-ai-review.yaml
PSEPK acnB gene review
The curated KT2440 review identifies Q88KF1 as a bifunctional aconitase with a core 2-methylisocitrate dehydratase/hydratase role in propionate assimilation.
file:PSEPK/prpD/prpD-uniprot.txt
UniProtKB entry Q88KF2 for PSEPK PrpD
UniProt records the direct 2-methylcitrate to 2-methyl-cis-aconitate dehydration reaction for Q88KF2.
file:PSEPK/prpF/prpF-uniprot.txt
UniProtKB entry Q88KF3 for PSEPK PrpF
UniProt places the PrpF-family aconitate isomerase Q88KF3 in propionate degradation.
file:projects/P_PUTIDA/deep-research/PSEPK__methylcitrate_cycle__ppu00640-deep-research-openscientist.md
OpenScientist PSEPK 2-methylcitrate-cycle pathway report
The pathway-level family and locus analysis resolves PP_2336 as AcnD, confirms that both dehydration implementations coexist in KT2440, and identifies both AcnA-I and AcnB as candidate enzymes for the common hydration step.
file:modules/methylcitrate_cycle-deep-research-openscientist.md
OpenScientist review of the 2-methylcitrate cycle
The generic module review supports modeling the direct PrpD and two-component AcnD/PrpF routes as alternative implementations that converge before a shared aconitase step. It also cautions that the exact AcnD product structure is not established uniformly across systems.
12Nodes
7Parts
2Variant Sets
4Variants
8Annotons
5Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • methylcitrate_cycle-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 (8/8 grounded genes reviewed)

8 complete review(s) · 8 with deep research · 0 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
acnA-I Q88L24 ✓ ✓ ✓
acnA-II Q88KF4 ✓ ✓ ✓
acnB Q88KF1 ✓ ✓ ✓
prpB Q88KF6 ✓ ✓ ✓
prpC Q88KF5 ✓ ✓ ✓
prpD Q88KF2 ✓ ✓ ✓
prpE Q88KD9 ✓ ✓ ✓
prpF Q88KF3 ✓ ✓ ✓

Details

2-methylcitrate cycleMetabolic Pathwaymethylcitrate_cycle
propionate catabolic processGO:0019543

The root is deliberately multi-part and taxon-neutral. Exact KT2440 accessions are used as representative members, not as a claim that the pathway is restricted to Pseudomonas. PrpD and AcnD/PrpF are modeled with ONE_OR_MORE semantics because organisms may encode either or both routes. The common hydration step likewise allows AcnA- and AcnB-family implementations, which may coexist in one genome. The AcnD product is deliberately represented generically because 4-methylaconitate is the leading assignment but exact structure and stereochemistry are not established uniformly across organisms.

Connections

Propionyl-CoA is the acyl donor for 2-methylcitrate synthesis.
2-methylcitrate enters either dehydration implementation.
Both alternatives converge on 2-methyl-cis-aconitate.
2-methylisocitrate is the substrate cleaved by PrpB.
Part 1: propionate activation
Propionate activation to propionyl-CoAReactionpropionate_activation

Annotons

Propionate-CoA ligase
propionate_coa_ligase
Participant: Family: PrpE-family propionate-CoA ligases
Family:
PrpE-family propionate-CoA ligases
Representative Members: PSEPK PrpEUniProtKB:Q88KD9

Function

propionate-CoA ligase activityGO:0050218
Substrates: propionate CoA ATP
Products: propionyl-CoA AMP diphosphate

Supplies the propionyl-CoA substrate used by 2-methylcitrate synthase; nonorthologous activation routes require separate pathway-instance adjudication.

Part 2: 2-methylcitrate formation
2-methylcitrate synthesisReactionmethylcitrate_synthesis

Annotons

2-methylcitrate synthase
methylcitrate_synthase
Participant: Family: PrpC 2-methylcitrate synthases
Family:
PrpC 2-methylcitrate synthases
Representative Members: PSEPK PrpCUniProtKB:Q88KF5

Function

2-methylcitrate synthase activityGO:0050440
Substrates: propionyl-CoA oxaloacetate H2O
Products: 2-methylcitrate CoA

Condenses propionyl-CoA and oxaloacetate to commit carbon to the cycle.

Part 3: 2-methyl-cis-aconitate generation
Conversion of 2-methylcitrate to 2-methyl-cis-aconitateMetabolic Pathwaymethylaconitate_generation

Alternative direct and two-component implementations produce the 2-methyl-cis-aconitate substrate used by the common hydration step.

Variant set: 2-methylcitrate dehydration implementations by reaction mechanism (One Or More)
Direct PrpD routeReactionprpD_direct_route

Annotons

PrpD 2-methylcitrate dehydratase
prpD_methylcitrate_dehydratase
Participant: Family: PrpD 2-methylcitrate dehydratases
Family:
PrpD 2-methylcitrate dehydratases
Representative Members: PSEPK PrpDUniProtKB:Q88KF2

Function

2-methylcitrate dehydratase activityGO:0047547
Substrates: 2-methylcitrate
Products: 2-methyl-cis-aconitate H2O

Directly dehydrates 2-methylcitrate to 2-methyl-cis-aconitate.

Two-component AcnD/PrpF routeMetabolic PathwayacnD_prpF_route

An aconitase-family dehydratase first forms a positional methylaconitate isomer, which PrpF rearranges to 2-methyl-cis-aconitate.

Connections

acnD_dehydration -> prpF_isomerization Provides Input For
The AcnD product is the substrate rearranged by PrpF.
Part 1: AcnD-dependent dehydration
AcnD-family 2-methylcitrate dehydrationReactionacnD_dehydration

Annotons

AcnD 2-methylcitrate dehydratase
acnD_pathway_dehydratase
Participant: Family: AcnD-family 2-methylcitrate dehydratases
Family:
AcnD-family 2-methylcitrate dehydratases
Representative Members: PSEPK AcnDUniProtKB:Q88KF4

Function

hydro-lyase activityGO:0016836
Substrates: 2-methylcitrate
Products: AcnD-derived methylaconitate isomer H2O
Cofactors: 4 iron, 4 sulfur cluster

Dehydrates 2-methylcitrate to the methylaconitate isomer used by PrpF. GO lacks an AcnD-specific product-resolved molecular-function term, so the available hydro-lyase parent is used.

Part 2: methylaconitate isomerization
PrpF methylaconitate isomerizationReactionprpF_isomerization

Annotons

PrpF aconitate isomerase
prpF_aconitate_isomerase
Participant: Family: PrpF methylaconitate isomerases
Family:
PrpF methylaconitate isomerases
Representative Members: PSEPK PrpFUniProtKB:Q88KF3

Function

isomerase activityGO:0016853
Substrates: AcnD-derived methylaconitate isomer
Products: 2-methyl-cis-aconitate

Converts the AcnD product to 2-methyl-cis-aconitate. GO lacks a methylaconitate-specific isomerase term, so the available isomerase parent is used.

Part 4: 2-methylisocitrate formation
2-methyl-cis-aconitate hydrationReactionmethylisocitrate_formation
Variant set: Aconitase-family hydration implementations by aconitase paralog family (One Or More)
AcnB-family hydrationReactionacnB_hydration_route

Annotons

AcnB-family 2-methylisocitrate hydratase
acnB_methylisocitrate_hydratase
Participant: Family: AcnB-family aconitate hydratases with methylisocitrate activity
Family:
AcnB-family aconitate hydratases with methylisocitrate activity
Representative Members: PSEPK AcnBUniProtKB:Q88KF1

Function

2-methylisocitrate dehydratase activityGO:0047456
Substrates: 2-methyl-cis-aconitate H2O
Products: 2-methylisocitrate
Cofactors: 4 iron, 4 sulfur cluster

Uses the reversible aconitase-family reaction in the hydration direction to form the PrpB substrate.

AcnA-family hydrationReactionacnA_hydration_route

Annotons

AcnA-family 2-methylisocitrate hydratase
acnA_methylisocitrate_hydratase
Participant: Family: AcnA-family aconitate hydratases with methylisocitrate activity
Family:
AcnA-family aconitate hydratases with methylisocitrate activity
Representative Members: PSEPK AcnA-IUniProtKB:Q88L24

Function

2-methylisocitrate dehydratase activityGO:0047456
Substrates: 2-methyl-cis-aconitate H2O
Products: 2-methylisocitrate
Cofactors: 4 iron, 4 sulfur cluster

Provides a second aconitase-family implementation of the reversible hydration step where AcnA retains this substrate range.

Part 5: carbon-carbon cleavage
2-methylisocitrate cleavageReactionmethylisocitrate_cleavage

Annotons

2-methylisocitrate lyase
methylisocitrate_lyase
Participant: Family: PrpB 2-methylisocitrate lyases
Family:
PrpB 2-methylisocitrate lyases
Representative Members: PSEPK PrpBUniProtKB:Q88KF6

Function

methylisocitrate lyase activityGO:0046421
Substrates: 2-methylisocitrate
Products: succinate pyruvate
Cofactors: magnesium ion

Cleaves 2-methylisocitrate to succinate and pyruvate, returning the oxaloacetate-derived carbon skeleton to central metabolism.