Aerobic phenylacetate catabolism

A reusable aerobic phenylacetyl-CoA pathway that activates phenylacetate, epoxidizes the aromatic ring with the multicomponent PaaABCE system, isomerizes and hydrolytically opens the ring, oxidizes the resulting semialdehyde, and processes the open-chain CoA ester through two thiolytic cleavages separated by a beta-oxidation-like hydration and oxidation sequence, yielding acetyl-CoA and succinyl-CoA. Regulatory and detoxification proteins are outside the required reaction chain.

MODULE:phenylacetate_catabolismDRAFTMetabolic Pathwaymodules/phenylacetate_catabolism.yaml

phenylacetate catabolic processGO:0010124

GO:0010124

phenylacetate catabolic process

GO:0010124 provides the biological-process boundary for conversion of phenylacetate through the aerobic phenylacetyl-CoA pathway.

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

OpenScientist research for the reusable aerobic phenylacetate catabolism module

The module-level review supports the ordered phenylacetyl-CoA pathway, the multicomponent epoxidase, bifunctional PaaZ, and the distinction between required reactions and accessory detoxification proteins.

file:projects/P_PUTIDA/deep-research/PSEPK__phenylacetate_catabolism__ppu00360-deep-research-openscientist.md

OpenScientist PSEPK ppu00360 pathway satisfiability review

The species-aware review finds the KT2440 pathway satisfiable, identifies paaJ as a gene omitted by the broad KEGG bucket, and separates the contiguous paa locus from paralogous beta-oxidation enzymes.

PMID:22961985

Protein-protein interactions in the β-oxidation part of the phenylacetate utilization pathway: crystal structure of the PaaF-PaaG hydratase-isomerase complex.

Structural work on E. coli identifies a stable PaaFG hydratase-isomerase complex, providing comparative evidence for interaction between the two crotonase-family enzymes.

file:PSEPK/paaK/paaK-uniprot.txt

UniProtKB entry Q88HS4 for PSEPK PaaK

UniProt identifies Q88HS4 as phenylacetate-CoA ligase, the activation step that supplies phenylacetyl-CoA.

file:PSEPK/paaA/paaA-uniprot.txt

UniProtKB entry Q88HS5 for PSEPK PaaA

UniProt places Q88HS5 in the ring 1,2-phenylacetyl-CoA epoxidase system.

file:PSEPK/paaZ/paaZ-uniprot.txt

UniProtKB entry Q88HT3 for PSEPK PaaZ

UniProt identifies Q88HT3 as the bifunctional oxepin-CoA hydrolase and semialdehyde dehydrogenase that opens and oxidizes the ring-cleavage intermediate.

file:PSEPK/paaJ/paaJ-uniprot.txt

UniProtKB entry Q88HS3 for PSEPK PaaJ

UniProt identifies Q88HS3 as a dual 3-oxoadipyl-CoA/3-oxo-5,6-dehydrosuberyl-CoA thiolase.

11Nodes

10Parts

0Variant Sets

0Variants

9Annotons

8Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

phenylacetate_catabolism-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 (10/10 grounded genes reviewed)

10 complete review(s) · 10 with deep research · 0 missing review · 0 reviewed but lacking deep research

Gene	Review	Complete	Deep research
paaA Q88HS5	✓	✓	✓
paaB Q88HS6	✓	✓	✓
paaC Q88HS7	✓	✓	✓
paaE Q88HS9	✓	✓	✓
paaF Q88HR9	✓	✓	✓
paaG Q88HS0	✓	✓	✓
paaH Q88HS1	✓	✓	✓
paaJ Q88HS3	✓	✓	✓
paaK Q88HS4	✓	✓	✓
paaZ Q88HT3	✓	✓	✓

Tree

Aerobic phenylacetate catabolismMetabolic Pathwayphenylacetate_catabolism

Parts
1. 1. phenylacetate activation
2. Phenylacetate activation to phenylacetyl-CoAReactionphenylacetate_activation
  
  Annotons
  - Phenylacetate-CoA ligase Family: phenylacetate-CoA ligases
3. 2. aromatic-ring epoxidation
4. Ring 1,2-phenylacetyl-CoA epoxidationReactionphenylacetyl_coa_epoxidation
  
  Annotons
  - PaaABCE phenylacetyl-CoA epoxidase system Protein Complex: PaaABCE phenylacetyl-CoA epoxidase system
5. 3. epoxide isomerization
6. PaaG epoxide isomerizationReactionpaaG_epoxide_isomerization
  
  Annotons
  - 1,2-epoxyphenylacetyl-CoA isomerase Family: PaaG 1,2-epoxyphenylacetyl-CoA isomerases
7. 4. hydrolytic ring opening and semialdehyde oxidation
8. Bifunctional PaaZ ring openingMetabolic PathwaypaaZ_ring_opening
  
  Parts
  1. 1. oxepin-CoA hydrolysis
  2. Oxepin-CoA hydrolysisReactionpaaZ_oxepin_hydrolysis
    
    Annotons
    
    PaaZ oxepin-CoA hydrolase Family: bifunctional PaaZ proteins
  3. 2. semialdehyde oxidation
  4. PaaZ semialdehyde oxidationReactionpaaZ_semialdehyde_oxidation
    
    Annotons
    
    PaaZ semialdehyde dehydrogenase Family: bifunctional PaaZ proteins
9. 5. first open-chain thiolysis
10. PaaJ 3-oxo-5,6-dehydrosuberyl-CoA thiolysisReactionpaaJ_dehydrosuberyl_thiolysis
  
  Annotons
  - PaaJ 3-oxo-5,6-dehydrosuberyl-CoA thiolase Family: PaaJ dual-intermediate thiolases
11. 6. open-chain enoyl-CoA hydration
12. PaaF open-chain hydrationReactionpaaF_hydration
  
  Annotons
  - PaaF enoyl-CoA hydratase Family: PaaF-family open-chain enoyl-CoA hydratases
13. 7. 3-hydroxyadipyl-CoA oxidation
14. PaaH 3-hydroxyadipyl-CoA oxidationReactionpaaH_dehydrogenation
  
  Annotons
  - PaaH 3-hydroxyacyl-CoA dehydrogenase Family: PaaH 3-hydroxyadipyl-CoA dehydrogenases
15. 8. 3-oxoadipyl-CoA thiolysis
16. PaaJ 3-oxoadipyl-CoA thiolysisReactionpaaJ_thiolysis
  
  Annotons
  - PaaJ 3-oxoadipyl-CoA thiolase Family: PaaJ dual-intermediate thiolases

Details

Aerobic phenylacetate catabolismMetabolic Pathwayphenylacetate_catabolism

phenylacetate catabolic processGO:0010124

Exact KT2440 accessions are representative members, not a species restriction. PaaD is a pathway-associated accessory protein but is not required by the minimal PaaABCE catalytic assembly in vitro; its proposed metallocenter maturation or assembly role remains unresolved and is not counted for module satisfiability. A stable PaaFG complex is known from E. coli, but obligate complex formation is not established across taxa, so PaaF and PaaG remain separate reaction annotons rather than a required complex selector. PaaI and PaaY thioesterases are pathway-associated proofreading or detoxification proteins, and PaaX is a regulator; none is a required reaction in this core linear module. Broad organism-level pathway maps are useful for candidate discovery, but the module boundary is the paa-specific phenylacetyl-CoA route.

Connections

phenylacetate_activation -> phenylacetyl_coa_epoxidation Provides Input For

PaaK supplies phenylacetyl-CoA to the epoxidase system.

phenylacetyl_coa_epoxidation -> paaG_epoxide_isomerization Provides Input For

The epoxidase product is rearranged by PaaG.

paaG_epoxide_isomerization -> paaZ_ring_opening Provides Input For

PaaG supplies the oxepin-CoA intermediate to PaaZ.

paaZ_ring_opening -> paaJ_dehydrosuberyl_thiolysis Provides Input For

PaaZ supplies the C8 beta-keto CoA ester for the first thiolytic shortening.

paaJ_dehydrosuberyl_thiolysis -> paaF_hydration Provides Input For

The first PaaJ cleavage supplies 2,3-dehydroadipyl-CoA to PaaF.

paaF_hydration -> paaH_dehydrogenation Provides Input For

PaaF produces 3-hydroxyadipyl-CoA for PaaH.

paaH_dehydrogenation -> paaJ_thiolysis Provides Input For

PaaH produces 3-oxoadipyl-CoA for PaaJ.

Part 1: phenylacetate activation

Phenylacetate activation to phenylacetyl-CoAReactionphenylacetate_activation

Annotons

Phenylacetate-CoA ligase

paaK_ligase

Participant: Family: phenylacetate-CoA ligases

Family:

phenylacetate-CoA ligases

Representative Members: PSEPK PaaKUniProtKB:Q88HS4

Function

phenylacetate-CoA ligase activityGO:0047475

Substrates: phenylacetate CoA ATP

Products: phenylacetyl-CoA AMP diphosphate

Activates phenylacetate for the oxygenase system.

Part 2: aromatic-ring epoxidation

Ring 1,2-phenylacetyl-CoA epoxidationReactionphenylacetyl_coa_epoxidation

Annotons

PaaABCE phenylacetyl-CoA epoxidase system

paaABCE_epoxidase_system

Participant: Protein Complex: PaaABCE phenylacetyl-CoA epoxidase system

Protein Complex:

PaaABCE phenylacetyl-CoA epoxidase system Minimal catalytic oxygenase assembly containing PaaA, PaaB, and PaaC oxygenase/accessory subunits together with the FAD-[2Fe-2S] PaaE reductase.

Active units:

PaaA alpha subunit

Participant: Family: PaaA epoxidase alpha subunits

Family:

PaaA epoxidase alpha subunits

Representative Members: PSEPK PaaAUniProtKB:Q88HS5

Role: Catalytic oxygenase alpha subunit.

PaaB regulatory subunit

Participant: Family: PaaB epoxidase regulatory subunits

Family:

PaaB epoxidase regulatory subunits

Representative Members: PSEPK PaaBUniProtKB:Q88HS6

Role: Regulatory/accessory subunit of the oxygenase system.

PaaC beta subunit

Participant: Family: PaaC epoxidase beta subunits

Family:

PaaC epoxidase beta subunits

Representative Members: PSEPK PaaCUniProtKB:Q88HS7

Role: Structural beta subunit that supports the PaaA-containing catalytic core.

PaaE reductase subunit

Participant: Family: PaaE epoxidase reductase subunits

Family:

PaaE epoxidase reductase subunits

Representative Members: PSEPK PaaEUniProtKB:Q88HS9

Role: Transfers reducing equivalents from NADPH through FAD and a [2Fe-2S] cluster.

Function:

oxidoreductase activityGO:0016491

Function

phenylacetyl-CoA 1,2-epoxidase activityGO:0097266

Substrates: phenylacetyl-CoA dioxygen NADPH

Products: 1,2-epoxyphenylacetyl-CoA NADP+ H2O

Activates the aromatic ring for nonoxygenolytic opening.

Part 3: epoxide isomerization

PaaG epoxide isomerizationReactionpaaG_epoxide_isomerization

Annotons

1,2-epoxyphenylacetyl-CoA isomerase

paaG_isomerase

Participant: Family: PaaG 1,2-epoxyphenylacetyl-CoA isomerases

Family:

PaaG 1,2-epoxyphenylacetyl-CoA isomerases

Representative Members: PSEPK PaaGUniProtKB:Q88HS0

Function

isomerase activityGO:0016853

Substrates: 1,2-epoxyphenylacetyl-CoA

Products: oxepin-CoA

Rearranges the epoxide to oxepin-CoA. GO currently provides only a broad isomerase term for this EC-defined activity.

Part 4: hydrolytic ring opening and semialdehyde oxidation

Bifunctional PaaZ ring openingMetabolic PathwaypaaZ_ring_opening

3-oxoadipyl-CoA thiolase activityGO:0033812

Substrates: 3-oxoadipyl-CoA CoA

Products: succinyl-CoA acetyl-CoA

Completes the pathway by thiolytic carbon-carbon cleavage.