phenylethylamine degradation I

MetaCyc:2PHENDEG-PWY

The complete two-step native pathway converts 2-phenylethylamine to phenylacetate in Escherichia coli K-12. The periplasmic copper/topaquinone-containing TynA homodimer oxidatively deaminates the amine, producing phenylacetaldehyde, ammonium and hydrogen peroxide; cytosolic FeaB oxidizes the aldehyde with NAD+. Rhea physiological charge forms and both complete equations are retained, including two protons in the FeaB product side. The aldehyde links the reactions across compartments; its transport mechanism is not specified. Downstream phenylacetate assimilation and the distinct quinohemoprotein degradation-II route are outside this exact native boundary. K-12 enzyme and mutant evidence is complemented by MG1655 transcription experiments and W3110 aerobic-growth measurements; the record does not imply expression or growth in every K-12 derivative or condition. FeaB is represented by its supported gene-product/activity association, without claiming an active isolated monomer or fixing the disputed oligomeric state: UniProt annotates a dimer, native MetaCyc a tetramer, and the inspected 2006 tetramer experiment used a supplied PadA construct whose exact equivalence to this K-12 protein was not established. The selected NAD+ route does not exclude reported NADP+ turnover. FeaR regulation is transcriptional and condition dependent; direct aldehyde binding to FeaR was not demonstrated in the inspected study.

Pathway type

aerobic aromatic amine catabolism

Organism scope

Escherichia coli K-12 NCBITaxon:83333

Read the source YAML

Pathway network

23 nodes · 27 asserted directed edges

Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.

Reaction / activity
Chemical / cofactor
Protein / complex
Cell / process context
Taxon
Pathway
Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

Show at full size (scroll to explore)

Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli K-12 `NCBITaxon:83333`	taxon
2-phenylethanaminium `CHEBI:225237`	small molecule
dioxygen `CHEBI:15379`	small molecule
water `CHEBI:15377`	small molecule
phenylacetaldehyde `CHEBI:16424`	small molecule
hydrogen peroxide `CHEBI:16240`	small molecule
ammonium `CHEBI:28938`	small molecule
NAD(1-) `CHEBI:57540`	small molecule
phenylacetate `CHEBI:18401`	small molecule
NADH(2-) `CHEBI:57945`	small molecule
hydron `CHEBI:15378`	small molecule
copper cation `CHEBI:23378`	cofactor
calcium(2+) `CHEBI:29108`	cofactor
L-topaquinone(1-) residue `CHEBI:79027`	cofactor
Primary amine oxidase `UniProtKB:P46883`	protein
Phenylacetaldehyde dehydrogenase `UniProtKB:P80668`	protein
Transcriptional activator FeaR `UniProtKB:Q47129`	protein
copper-containing amine oxidase `MetaCyc:AMINEOXID-CPLX`	complex
periplasmic space `GO:0042597`	cellular component
cytosol `GO:0005829`	cellular component
2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	molecular activity	left to right
2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	molecular activity	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
2-phenylethanaminium `CHEBI:225237`	consumes	2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	RHEA:25266 Source assertion: The directed Rhea reaction places CHEBI:225237 on its substrates side with coefficient 1. Source location `http://rdf.rhea-db.org/25266/rh:substrates -> http://rdf.rhea-db.org/25265_L/rh:contains1 -> http://rdf.rhea-db.org/Participant_25265_compound_4466/rh:compound -> http://rdf.rhea-db.org/Compound_4466/rh:chebi`
dioxygen `CHEBI:15379`	consumes	2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	RHEA:25266 Source assertion: The directed Rhea reaction places CHEBI:15379 on its substrates side with coefficient 1. Source location `http://rdf.rhea-db.org/25266/rh:substrates -> http://rdf.rhea-db.org/25265_L/rh:contains1 -> http://rdf.rhea-db.org/Participant_25265_compound_1198/rh:compound -> http://rdf.rhea-db.org/Compound_1198/rh:chebi`
water `CHEBI:15377`	consumes	2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	RHEA:25266 Source assertion: The directed Rhea reaction places CHEBI:15377 on its substrates side with coefficient 1. Source location `http://rdf.rhea-db.org/25266/rh:substrates -> http://rdf.rhea-db.org/25265_L/rh:contains1 -> http://rdf.rhea-db.org/Participant_25265_compound_1283/rh:compound -> http://rdf.rhea-db.org/Compound_1283/rh:chebi`
2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	produces	phenylacetaldehyde `CHEBI:16424`	RHEA:25266 Source assertion: The directed Rhea reaction places CHEBI:16424 on its products side with coefficient 1. Source location `http://rdf.rhea-db.org/25266/rh:products -> http://rdf.rhea-db.org/25265_R/rh:contains1 -> http://rdf.rhea-db.org/Participant_25265_compound_2222/rh:compound -> http://rdf.rhea-db.org/Compound_2222/rh:chebi`
2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	produces	hydrogen peroxide `CHEBI:16240`	RHEA:25266 Source assertion: The directed Rhea reaction places CHEBI:16240 on its products side with coefficient 1. Source location `http://rdf.rhea-db.org/25266/rh:products -> http://rdf.rhea-db.org/25265_R/rh:contains1 -> http://rdf.rhea-db.org/Participant_25265_compound_3075/rh:compound -> http://rdf.rhea-db.org/Compound_3075/rh:chebi`
2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	produces	ammonium `CHEBI:28938`	RHEA:25266 Source assertion: The directed Rhea reaction places CHEBI:28938 on its products side with coefficient 1. Source location `http://rdf.rhea-db.org/25266/rh:products -> http://rdf.rhea-db.org/25265_R/rh:contains1 -> http://rdf.rhea-db.org/Participant_25265_compound_1012/rh:compound -> http://rdf.rhea-db.org/Compound_1012/rh:chebi`
phenylacetaldehyde `CHEBI:16424`	consumes	2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	RHEA:21393 Source assertion: The directed Rhea reaction places CHEBI:16424 on its substrates side with coefficient 1. Source location `http://rdf.rhea-db.org/21393/rh:substrates -> http://rdf.rhea-db.org/21392_L/rh:contains1 -> http://rdf.rhea-db.org/Participant_21392_compound_2222/rh:compound -> http://rdf.rhea-db.org/Compound_2222/rh:chebi`
NAD(1-) `CHEBI:57540`	consumes	2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	RHEA:21393 Source assertion: The directed Rhea reaction places CHEBI:57540 on its substrates side with coefficient 1. Source location `http://rdf.rhea-db.org/21393/rh:substrates -> http://rdf.rhea-db.org/21392_L/rh:contains1 -> http://rdf.rhea-db.org/Participant_21392_compound_3484/rh:compound -> http://rdf.rhea-db.org/Compound_3484/rh:chebi`
water `CHEBI:15377`	consumes	2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	RHEA:21393 Source assertion: The directed Rhea reaction places CHEBI:15377 on its substrates side with coefficient 1. Source location `http://rdf.rhea-db.org/21393/rh:substrates -> http://rdf.rhea-db.org/21392_L/rh:contains1 -> http://rdf.rhea-db.org/Participant_21392_compound_1283/rh:compound -> http://rdf.rhea-db.org/Compound_1283/rh:chebi`
2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	produces	phenylacetate `CHEBI:18401`	RHEA:21393 Source assertion: The directed Rhea reaction places CHEBI:18401 on its products side with coefficient 1. Source location `http://rdf.rhea-db.org/21393/rh:products -> http://rdf.rhea-db.org/21392_R/rh:contains1 -> http://rdf.rhea-db.org/Participant_21392_compound_5243/rh:compound -> http://rdf.rhea-db.org/Compound_5243/rh:chebi`
2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	produces	NADH(2-) `CHEBI:57945`	RHEA:21393 Source assertion: The directed Rhea reaction places CHEBI:57945 on its products side with coefficient 1. Source location `http://rdf.rhea-db.org/21393/rh:products -> http://rdf.rhea-db.org/21392_R/rh:contains1 -> http://rdf.rhea-db.org/Participant_21392_compound_1650/rh:compound -> http://rdf.rhea-db.org/Compound_1650/rh:chebi`
2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	produces	hydron `CHEBI:15378`	RHEA:21393 Source assertion: The directed Rhea reaction places CHEBI:15378 on its products side with coefficient 2. Source location `http://rdf.rhea-db.org/21393/rh:products -> http://rdf.rhea-db.org/21392_R/rh:contains2 -> http://rdf.rhea-db.org/Participant_21392_compound_3249/rh:compound -> http://rdf.rhea-db.org/Compound_3249/rh:chebi`
copper-containing amine oxidase `MetaCyc:AMINEOXID-CPLX`	has_part	Primary amine oxidase `UniProtKB:P46883`	MetaCyc:AMINEOXID-CPLX Source assertion: The native TynA assembly contains two AMINEOXID-MONOMER subunits. Source location `Protein[@frameid="AMINEOXID-CPLX"]/component[Protein/@frameid="AMINEOXID-MONOMER"]/coefficient=2` MetaCyc:AMINEOXID-MONOMER Source assertion: The native subunit has an explicit UniProt unification cross-reference to P46883. Source location `Protein[@frameid="AMINEOXID-MONOMER"]/dblink[dblink-db="UNIPROT" and dblink-oid="P46883"]` UniProtKB:P46883 Source assertion: UniProt records a homodimer, with experimental evidence codes tied to PMID10387067,10576737 and9048544. Source location `comments[commentType="SUBUNIT"]/texts`
copper-containing amine oxidase `MetaCyc:AMINEOXID-CPLX`	catalyzes	2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	MetaCyc:AMINEOXID-CPLX Source assertion: Native AMINEPHEN-ENZRXN links this assembly to the phenylethylamine oxidation step. Source location `Protein[@frameid="AMINEOXID-CPLX"]/catalyzes/Enzymatic-Reaction[@frameid="AMINEPHEN-ENZRXN"]/reaction` UniProtKB:P46883 Source assertion: UniProt experimentally annotates TynA phenylethylamine oxidation and maps it to RHEA:25265. Source location `comments[commentType="CATALYTIC ACTIVITY"]/reaction[reactionCrossReferences/id="RHEA:25265"]` RHEA:25266 Source assertion: Rhea142 explicitly links master RHEA:25265 to directional reaction RHEA:25266. Source location `http://rdf.rhea-db.org/25265/rh:directionalReaction -> http://rdf.rhea-db.org/25266`
Phenylacetaldehyde dehydrogenase `UniProtKB:P80668`	enables Gene-product/activity association; no isolated-monomer catalysis or fixed oligomer stoichiometry is asserted. The native tetramer and UniProt dimer assignments remain explicitly discordant.	2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	UniProtKB:P80668 Source assertion: UniProt associates K-12 FeaB with phenylacetaldehyde oxidation by NAD+ in RHEA:21392. Source location `comments[commentType="CATALYTIC ACTIVITY"]/reaction[reactionCrossReferences/id="RHEA:21392"]` PMID:9043126 Source assertion: The K-12 study located the PAD gene and assayed purified PAD against phenylacetaldehyde. Source location `resultList/result[id="9043126"]/abstractText` RHEA:21393 Source assertion: Rhea142 explicitly links master RHEA:21392 to directional reaction RHEA:21393. Source location `http://rdf.rhea-db.org/21392/rh:directionalReaction -> http://rdf.rhea-db.org/21393`
Primary amine oxidase `UniProtKB:P46883`	has_cofactor	copper cation `CHEBI:23378`	UniProtKB:P46883 Source assertion: Copper binding is experimentally annotated; the entry reports one copper ion per subunit. Source location `comments[commentType="COFACTOR"]/cofactors[cofactorCrossReference/id="CHEBI:23378"]; associated note/texts and ECO:0000269 evidence`
Primary amine oxidase `UniProtKB:P46883`	has_cofactor	calcium(2+) `CHEBI:29108`	UniProtKB:P46883 Source assertion: Calcium binding is experimentally annotated; the entry reports two calcium ions per subunit. Source location `comments[commentType="COFACTOR"]/cofactors[cofactorCrossReference/id="CHEBI:29108"]; associated note/texts and ECO:0000269 evidence`
Primary amine oxidase `UniProtKB:P46883`	has_cofactor	L-topaquinone(1-) residue `CHEBI:79027`	UniProtKB:P46883 Source assertion: One covalently integrated topaquinone residue per subunit is experimentally annotated; this is not a freely consumed small molecule. Source location `comments[commentType="COFACTOR"]/cofactors[cofactorCrossReference/id="CHEBI:79027"]; associated note/texts and ECO:0000269 evidence`
Primary amine oxidase `UniProtKB:P46883`	located_in	periplasmic space `GO:0042597`	UniProtKB:P46883 Source assertion: UniProt locates TynA in the periplasm. Source location `comments[commentType="SUBCELLULAR LOCATION"]/subcellularLocations/location[value="Periplasm"]`
2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	occurs_in	periplasmic space `GO:0042597`	PMID:23913322 Source assertion: The W3110 study identifies the amine oxidase reaction as periplasmic and measures peroxide formation during aerobic PEA use. Source location `Introduction; Results, E.coli can utilize phenylethylamine as sole carbon or nitrogen source; Fig.1`
Phenylacetaldehyde dehydrogenase `UniProtKB:P80668`	located_in	cytosol `GO:0005829`	PMID:24013633 Source assertion: FeaB is identified as the cytosolic NAD-linked aldehyde dehydrogenase. Source location `Introduction, first paragraph; Fig.1A`
2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	occurs_in	cytosol `GO:0005829`	PMID:24013633 Source assertion: The pathway description places FeaB-mediated aldehyde oxidation in the cytosol. Source location `Introduction, first paragraph; Fig.1A`
2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	provides_input_for The shared aldehyde is transferred between cellular compartments; no transporter or transport reaction is inferred.	2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	MetaCyc:2PHENDEG-PWY Source assertion: AMINEPHEN-RXN precedes PHENDEHYD-RXN through shared phenylacetaldehyde in the exact two-step native pathway. Source location `Pathway[@frameid="2PHENDEG-PWY"]/reaction-ordering; reaction-layout` PMID:3309152 Source assertion: K-12 converts the amine through phenylacetaldehyde to phenylacetate using successive oxidase and NAD-dependent dehydrogenase activities. Source location `resultList/result[id="3309152"]/abstractText`
2-phenylethylamine + O2 + H2O => 2-phenylacetaldehyde + H2O2 + NH4(+) `RHEA:25266`	part_of	`MetaCyc:2PHENDEG-PWY`	MetaCyc:2PHENDEG-PWY Source assertion: The complete native reaction-list includes AMINEPHEN-RXN; its pathway layout selects the left-to-right catabolic direction. Source location `Pathway[@frameid="2PHENDEG-PWY"]/reaction-list; reaction-layout[Reaction/@frameid="AMINEPHEN-RXN"]` MetaCyc:AMINEPHEN-RXN Source assertion: The native AMINEPHEN-RXN explicitly unifies this reaction with RHEA:25266. Source location `Reaction[@frameid="AMINEPHEN-RXN"]/dblink[dblink-db="RHEA" and dblink-oid="25266"]`
2-phenylacetaldehyde + NAD(+) + H2O => 2-phenylacetate + NADH + 2 H(+) `RHEA:21393`	part_of	`MetaCyc:2PHENDEG-PWY`	MetaCyc:2PHENDEG-PWY Source assertion: The complete native reaction-list includes PHENDEHYD-RXN; its pathway layout selects the left-to-right catabolic direction. Source location `Pathway[@frameid="2PHENDEG-PWY"]/reaction-list; reaction-layout[Reaction/@frameid="PHENDEHYD-RXN"]` MetaCyc:PHENDEHYD-RXN Source assertion: The native PHENDEHYD-RXN cross-reference identifies bidirectional RHEA:21395. The reaction object is annotated REVERSIBLE. Source location `Reaction[@frameid="PHENDEHYD-RXN"]/dblink[dblink-db="RHEA" and dblink-oid="21395"]; reaction-direction` RHEA:21393 Source assertion: Rhea142 links master RHEA:21392 to both bidirectional RHEA:21395 and forward RHEA:21393, preserving the same underlying reaction. Source location `http://rdf.rhea-db.org/21392/rh:bidirectionalReaction -> http://rdf.rhea-db.org/21395; rh:directionalReaction -> http://rdf.rhea-db.org/21393`
`MetaCyc:2PHENDEG-PWY`	part_of K-12 pathway context supported by specific experimental strains; this does not claim constitutive activity in every K-12 derivative.	Escherichia coli K-12 `NCBITaxon:83333`	PMID:3309152 Source assertion: K-12 cultures use this amine-to-phenylacetate route; PAD-defective mutants lose carbon-source utilization but retain nitrogen-source utilization. Source location `resultList/result[id="3309152"]/abstractText` PMID:9043126 Source assertion: The K-12 PAD, amine-oxidase and positive-regulator genes were mapped and their pathway roles examined. Source location `resultList/result[id="9043126"]/abstractText`
Transcriptional activator FeaR `UniProtKB:Q47129`	regulates Transcriptional regulation under tested nutrient and inducer conditions, not direct allosteric activation of either enzyme.	`MetaCyc:2PHENDEG-PWY`	UniProtKB:Q47129 Source assertion: FeaR is annotated as a positive regulator of tynA/maoA and feaB/padA expression. Source location `comments[commentType="FUNCTION"]/texts` PMID:24013633 Source assertion: Under carbon limitation with a pathway inducer, FeaR-dependent transcription activates both tynA and feaB; nitrogen limitation induces tynA without the same feaB response. Source location `Results, Regulation of the feaB and tynA promoters; Discussion; Fig.9`

References

RHEA:25266 Rhea directed reaction 25266 (source version: Rhea142; release2026-09-02; digest covers complete native RDF gzip, selected objects identified in source locators)
RHEA:21393 Rhea directed reaction 21393 (source version: Rhea142; release2026-09-02; digest covers complete native RDF gzip, selected objects identified in source locators)
UniProtKB:P46883 UniProtKB P46883: Primary amine oxidase (source version: Retrieved2026-10-11; entryVersion 206; sequenceVersion 1; annotation date 2026-06-10)
UniProtKB:P80668 UniProtKB P80668: Phenylacetaldehyde dehydrogenase (source version: Retrieved2026-10-11; entryVersion 175; sequenceVersion 2; annotation date 2026-09-02)
UniProtKB:Q47129 UniProtKB Q47129: Transcriptional activator FeaR (source version: Retrieved2026-10-11; entryVersion 165; sequenceVersion 1; annotation date 2026-09-02)
MetaCyc:2PHENDEG-PWY MetaCyc 2PHENDEG-PWY: phenylethylamine degradation I (source version: MetaCyc22.5 native META frame; retrieved2026-10-11)
MetaCyc:AMINEOXID-CPLX MetaCyc AMINEOXID-CPLX: copper-containing amine oxidase (source version: MetaCyc22.5 native META frame; retrieved2026-10-11)
MetaCyc:AMINEOXID-MONOMER MetaCyc AMINEOXID-MONOMER: copper-containing amine oxidase subunit (source version: MetaCyc22.5 native META frame; retrieved2026-10-11)
MetaCyc:PHENDEHYD-RXN MetaCyc PHENDEHYD-RXN: phenylacetaldehyde dehydrogenase reaction (source version: MetaCyc22.5 native META frame; retrieved2026-10-11)
PMID:3309152 2-Phenylethylamine catabolism by Escherichia coli K12. (source version: Europe PMC core primary-article abstract record; retrieved2026-10-11; digest covers complete six-result JSON response)
PMID:9043126 2-phenylethylamine catabolism by Escherichia coli K-12: gene organization and expression. (source version: Europe PMC core primary-article abstract record; retrieved2026-10-11; digest covers complete six-result JSON response)
PMID:24013633 Finely Tuned Regulation of the Aromatic Amine Degradation Pathway in Escherichia coli (source version: Complete PMC primary full-text HTML; retrieved2026-10-11)
PMID:23913322 How Escherichia coli Tolerates Profuse Hydrogen Peroxide Formation by a Catabolic Pathway (source version: Complete PMC primary full-text HTML; retrieved2026-10-11)
MetaCyc:AMINEPHEN-RXN MetaCyc AMINEPHEN-RXN: phenylethylamine oxidation reaction (source version: MetaCyc22.5 native META frame; retrieved2026-10-11)

Curation history

2026-10-11T03:53:27Z Codex
- CREATE — Add the complete two-step phenylethylamine degradation I pathway.
  Retained current charge-balanced Rhea reactions, TynA assembly and cofactors, compartments and conditional FeaR regulation. Preserved FeaB assembly uncertainty without omitting its supported activity. Source dossiers and verification receipts are in research/pathway_additions/2026-10-11-next-186; independent scientific assessments are saved separately.
Read this curation session