Definition of L-phenylalanine catabolism
As rules and steps, or see full text
Rules
Overview: Phenylalanine utilization in GapMind is based on MetaCyc pathway L-phenylalanine degradation I (aerobic, via tyrosine, link), pathway II (anaerobic, via phenylacetaldehyde dehydrogenase, link), degradation via phenylpyruvate:ferredoxin oxidoreductase (PMC3346364), or degradation via phenylacetaldehyde:ferredoxin oxidoreductase (PMID:24214948). (MetaCyc describes additional pathways, but they do not result in carbon incorporation or are not reported in prokaryotes, so they are not included in GapMind.)
- all:
- phenylalanine-transport, ARO8, phenylpyruvate-fd-oxidoreductase and phenylacetyl-CoA-degradation
- or phenylalanine-transport, ARO8, phenylpyruvate-decarboxylase, pad-dh and phenylacetate-degradation
- or phenylalanine-transport, ARO8, phenylpyruvate-decarboxylase, pfor and phenylacetate-degradation
- or phenylalanine-transport, PAH, PCBD, QDPR and tyrosine-degradation
- Comment: Phenylalanine can be catabolized via transaminase ARO8, which forms phenylpyruvate (also known as 3-phenyl-2-oxo-propanoate), and phenylpyruvate:ferredoxin oxidoreductase, which forms phenylacetyl-CoA. In the anaerobic pathway, the transaminase ARO8 forms phenylpyruvate, a carboxy-lyase forms phenylacetaldehyde, and a dehydrogenase (pad-dh) forms phenylacetate Or, in a variation on the anaerobic pathway, the phenylacetaldehyde is oxidized to phenylacetate by phenylacetaldehyde:ferredoxin oxidoreductase (pfor). In the aerobic pathway, PAH forms tyrosine and hydroxylates its tetrahydropterin co-substrate; the tetrahydropterin is regenerated by dehydratase PCBD and reductase QDPR.
- phenylpyruvate-fd-oxidoreductase:
- iorA and iorB
- or iorAB
- Comment: This enzyme is usually known as indolepyruvate:ferredoxin oxidoreductase, but it acts on phenylpyruvate as well, forming phenylacetyl-CoA (PMID:8206994). Phenylpyruvate:ferredoxin oxidoreductase has both heterodimeric (iorA/iorB) and fused (iorAB) forms.
- phenylpyruvate-decarboxylase:
- ARO10
- or PPDCalpha and PPDCbeta
- Comment: Phenylpyruvate can be decarboxylated to phenylacetaldehyde by the typical homomeric enzyme, or by a heterodimer reported in Streptomyces virginiae (see PMID:28719183)
- phenylacetyl-CoA-degradation:
- paaA, paaB, paaC, paaE, paaG, paaZ1, paaZ2, paaJ1, paaF, paaH and paaJ2
- or phenylacetyl-CoA-dehydrogenase, phenylglyoxylate-dehydrogenase and benzoyl-CoA-degradation
- Comment: In the aerobic pathway, oxygen-dependent 1,2-epoxidase (PaaABCE) converts phenylacetyl-CoA to 1,2-epoxyphenylacetyl-CoA, which spontaenously rearranges to 2-(oxepinyl)acetyl-CoA; isomerase PaaG forms 2-oxepin-2(3H)-ylideneacetyl-CoA ("oxepin-CoA"); a ring-opening hydrolase forms 3-oxo-5,6-didehydrosuberyl-CoA semialdehyde; a dehydrogenase forms 3-oxo-5,6-didehydrosuberyl-CoA; thiolase PaaJ forms cis-3,4-didehydroadipyl-CoA (and acetyl-CoA); isomerase PaaG forms trans-2,3-didehydroadipyl-CoA; hydratase PaaF forms (3S)-hydroxyadipyl-CoA; dehydrogenase PaaH forms 3-oxoadipyl-CoA, and thiolase PaaJ forms succinyl-CoA and acetyl-CoA. (The role of PaaG is described in PMID:31689071 and differs slightly from MetaCyc.) In the anaerobic pathway, a dehydrogenase forms phenylglyoxyl-CoA, a hydrolase forms phenylglyoxylate (this step is not linked to sequence but is likely provided by the phenylglyoxylyl-CoA dehydrogenase, see PMID:10336636), and another dehydrogenase forms benzoyl-CoA and CO2. In principle, this pathway could occur aerobically, so GapMind includes aerobic pathways for degrading the benzoyl-CoA.
- phenylacetate-degradation: paaK and phenylacetyl-CoA-degradation
- Comment: Phenylacetate is activated to phenylacetyl-CoA by paaK
- benzoyl-CoA-degradation:
- benzoyl-CoA-reductase, dch, had, oah, pimB and glutaryl-CoA-degradation
- or benzoyl-CoA-reductase, Ch1CoA, badK, badH, badI, pimD, pimC, pimF and glutaryl-CoA-degradation
- or boxA, boxB, boxC, boxD, paaF, paaH and paaJ2
- Comment: Benzoyl-CoA can be degraded anaerobically (link) by reduction to cyclohex-1,5-diene-1-carbonyl-CoA, followed by hydratase (dch) to 6-hydroxycyclohex-1-ene-1-carbonyl-CoA, a dehydrogenase to 6-oxocyclohex-1-ene-1-carbonyl-CoA, a hydrolase to 2-hydroxy-6-oxocycloheane-1-carbonyl-CoA, a ring-opening hydrolase to 3-hydroxypimeloyl-CoA [the last two steps are both catalyzed by oah], a dehydrogenase to 3-oxopimeloyl-CoA [not linked to sequence and omitted], and an acetyltransferase to glutaryl-CoA and acetyl-CoA. Alternatively, after reduction to cyclohex-1,5-diene-1-carbonyl-CoA, Ch1CoA can further reduce it to cyclohex-1-ene-1-carboxyl-CoA (link), followed by hydration to 2-hydroxy-cyclohexane-1-carbonyl-CoA, oxidation to 2-ketocyclohexane-1-carbonyl-CoA, cleavage by a ring-opening hydrolase to pimeloyl-CoA, oxidation to 2,3-didehydropimeloyl-CoA, hydration to 3-hydroxypimeloyl-C, oxidation to 3-oxopimeloyl-CoA and cleavage by a thiolase to glutaryl-CoA and acetyl-CoA. Benzoyl-CoA degradation can be degraded aerobically (link) by an epoxidase (boxAB) that forms 2,3-epoxy-2-3-dihydrobenzoyl-CoA; a dihydrolase forms cis-3,4-dihydroadipyl-CoA semialdehyde and formate; a dehydrogenase forms cis-3,4-dehydroadipyl-CoA; and an unknown isomerase forms trans-2,3-dehydroadipyl-CoA. This is converted to succinyl-CoA as in the anaerobic pathway (paaF, paaH, and paaJ2).
- phenylglyoxylate-dehydrogenase: padG, padI, padE, padF and padH
- phenylacetyl-CoA-dehydrogenase: padB, padC and padD
- glutaryl-CoA-degradation: gcdH, ech, fadB and atoB
- Comment: In MetaCyc pathway glutaryl-CoA degradation (link), glutaryl-CoA is oxidized to (E)-glutaconyl-CoA and oxidatively decarboxylated to crotonyl-CoA (both by the same enzyme), hydrated to 3-hydroxybutanoyl-CoA, oxidized to acetoacetyl-CoA, and cleaved to two acetyl-CoA.
- benzoyl-CoA-reductase:
- bcrA, bcrB, bcrC and bcrD
- or bamB, bamC, bamD, bamE, bamF, bamG, bamH and bamI
- Comment: Benzoyl-CoA reduction is energetically unfavorable. There are two classes of reductases: class I enzymes (bcrABCD) use ATP to drive the reaction, while class II enzymes (bamBCDEFGHI) are thought to us an electron bifurcation. SYN_02587 (Q2LQN9) from Syntrophus aciditrophicus, which can oxidize cyclohex-1,5-diene-1-carbonyl-CoA to benzoyl-CoA, is not included because it seems to lack a mechanism to drive benzoyl-CoA reduction.
- tyrosine-degradation: HPD, hmgA, maiA, fahA and acetoacetate-degradation
- Comment: In pathway I, an aminotransferase (not represented) forms 3-(4-hydroxyphenyl)pyruvate, dioxygenase HPD forms homogentisate, another oxygenase forms 4-maleyl-acetoacetate, an isomerase forms 4-fumaryl-acetoacetate, and a hydrolase yields acetoacetate and fumarate. (Fumarate is part of the TCA cycle so its catabolism is not described.)
- acetoacetate-degradation: acetoacetate-activation and atoB
- Comment: The acetoacetate is activated to acetoacetyl-CoA, and cleaved by acetyl-CoA acetyltransferase, giving two acetyl-CoA.
- acetoacetate-activation:
- atoA and atoD
- or aacS
- Comment: acetyl-CoA:acetoacetyl-CoA transferase (sometimes given EC 2.8.3.9 or EC 2.8.3.8) or succinyl-CoA:acetoacetyl-CoA transferase (EC 2.8.3.5, also known as 3-oxoacid CoA-transferase) can activate acetoacetate. These have an A and B subunit. Alternatively, an ATP-dependent ligase (aacS) can activate acetoacetate (EC 6.2.1.16).
- phenylalanine-transport:
- livF, livG, livH, livM and livJ
- or aroP
- Comment: Transporters were identified using query: transporter:phenylalanine:L-phenylalanine:phe
Steps
livF: L-phenylalanine ABC transporter, ATPase component 1 (LivF)
- Curated sequence CH_003736: high-affinity branched-chain amino acid ABC transporter, ATP-binding protein LivF. LivF aka B3454, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter ATP binding subunit LivF (EC 7.4.2.2). branched chain amino acid/phenylalanine ABC transporter ATP binding subunit LivF (EC 7.4.2.2)
- UniProt sequence A0A159ZWL6: RecName: Full=High-affinity branched-chain amino acid transport ATP-binding protein {ECO:0000256|PIRNR:PIRNR039137};
- Ignore hits to P21630 when looking for 'other' hits (High-affinity branched-chain amino acid transport ATP-binding protein BraG, component of Branched chain amino acid uptake transporter. Transports alanine)
- UniProt sequence A0A165KC78: SubName: Full=ABC transporter ATP-binding protein {ECO:0000313|EMBL:KZT15317.1};
- Total: 3 characterized proteins
livG: L-phenylalanine ABC transporter, ATPase component 2 (LivG)
- Curated sequence P0A9S7: High-affinity branched-chain amino acid transport ATP-binding protein LivG aka B3455, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter ATP binding subunit LivG (EC 7.4.2.2). branched chain amino acid/phenylalanine ABC transporter ATP binding subunit LivG (EC 7.4.2.2)
- UniProt sequence A0A159ZWS6: SubName: Full=High-affinity branched-chain amino acid ABC transporter ATP-binding protein LivG {ECO:0000313|EMBL:AMZ72285.1};
- Ignore hits to P21629 when looking for 'other' hits (High-affinity branched-chain amino acid transport ATP-binding protein BraF, component of Branched chain amino acid uptake transporter. Transports alanine)
- UniProt sequence A0A165KC86: SubName: Full=ABC transporter ATP-binding protein {ECO:0000313|EMBL:KZT15318.1};
- Total: 3 characterized proteins
livH: L-phenylalanine ABC transporter, permease component 1 (LivH)
- Curated sequence LIVH-MONOMER: branched chain amino acid/phenylalanine ABC transporter membrane subunit LivH (EC 7.4.2.2). high-affinity branched-chain amino acid ABC transporter, permease protein LivH. High-affinity branched-chain amino acid transport system permease protein LivH aka B3457, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter membrane subunit LivH (EC 7.4.2.2)
- UniProt sequence A0A0D9B2B6: SubName: Full=Branched-chain amino acid ABC transporter permease LivH {ECO:0000313|EMBL:AMZ72283.1}; SubName: Full=Branched-chain amino acid transporter permease subunit LivH {ECO:0000313|EMBL:KJH87425.1}; SubName: Full=L-leucine ABC transporter membrane protein /L-isoleucine ABC transporter membrane protein /L-valine ABC transporter membrane protein {ECO:0000313|EMBL:TCV66884.1};
- Ignore hits to P21627 when looking for 'other' hits (High-affinity branched-chain amino acid transport system permease protein BraD, component of Branched chain amino acid uptake transporter. Transports alanine)
- UniProt sequence A0A165KC95: SubName: Full=ABC transporter permease {ECO:0000313|EMBL:KZT15319.1};
- Total: 3 characterized proteins
livM: L-phenylalanine ABC transporter, permease component 2 (LivM)
- Curated sequence P22729: High-affinity branched-chain amino acid transport system permease protein LivM; LIV-I protein M. LivM aka B3456, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter membrane subunit LivM (EC 7.4.2.2). branched chain amino acid/phenylalanine ABC transporter membrane subunit LivM (EC 7.4.2.2)
- UniProt sequence A0A159ZYE0: SubName: Full=High-affinity branched-chain amino acid ABC transporter permease LivM {ECO:0000313|EMBL:AMZ72284.1};
- Ignore hits to P21628 when looking for 'other' hits (High-affinity branched-chain amino acid transport system permease protein BraE, component of Branched chain amino acid uptake transporter. Transports alanine)
- UniProt sequence A0A165KER0: SubName: Full=ABC transporter ATP-binding protein {ECO:0000313|EMBL:KZT15410.1};
- Total: 3 characterized proteins
livJ: L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK
- Curated sequence CH_107418: leucine-specific-binding protein LivK. Livk aka B3458, component of Leucine; leucine/isoleucine/valine porter. L-leucine/L-phenylalanine ABC transporter periplasmic binding protein (EC 7.4.2.2). L-leucine/L-phenylalanine ABC transporter periplasmic binding protein (EC 7.4.2.2)
- Curated sequence P0AD96: Leu/Ile/Val-binding protein LivJ aka B3460 aka LIV-BP, component of Leucine; leucine/isoleucine/valine porter. branched chain amino acid/phenylalanine ABC transporter periplasmic binding protein (EC 7.4.2.2). branched chain amino acid/phenylalanine ABC transporter periplasmic binding protein (EC 7.4.2.2)
- UniProt sequence A0A160A0J6: SubName: Full=Leucine ABC transporter subunit substrate-binding protein LivK {ECO:0000313|EMBL:AMZ72282.1};
- Ignore hits to P21175 when looking for 'other' hits (Leucine-, isoleucine-, valine-, threonine-, and alanine-binding protein; LIVAT-BP; Leu/Ile/Val/Thr/Ala-binding protein. Leucine-, isoleucine-, valine-, threonine-, and alanine-binding protein, component of Branched chain amino acid uptake transporter. Transports alanine)
- UniProt sequence A0A165KTD4: SubName: Full=Branched chain amino acid ABC transporter substrate-binding protein {ECO:0000313|EMBL:KZT16064.1};
- Total: 4 characterized proteins
aroP: L-phenylalanine:H+ symporter AroP
- Curated sequence P15993: Aromatic amino acid:H+ symporter, AroP of 457 aas and 12 TMSs (Cosgriff and Pittard 1997). Transports phenylalanine, tyrosine and tryptophan. aromatic amino acid:H+ symporter AroP. aromatic amino acid:H+ symporter AroP
- Curated sequence F2HN33: Transporter for phenylalainine, tyrosine and tryptophan of 449 aas and 12 TMSs, FywP or YsjA
- Curated sequence P24207: Phenylalanine:H+ symporter, PheP of 458 aas and 12 established TMSs. phenylalanine:H+ symporter PheP. phenylalanine:H+ symporter PheP
- Curated sequence Q2VQZ4: Arbuscular mycorrhizal fungal proline:H+ symporter, AAP1 (binds and probably transports nonpolar, hydrophobic amino acids)
- Curated sequence Q46065: Aromatic amino acid permease, AroP
- UniProt sequence A0A0C4YP23: SubName: Full=Aromatic amino acid transport protein AroP {ECO:0000313|EMBL:AJG24240.1};
- Ignore hits to A2RMP5 when looking for 'other' hits (Aromatic amino acid permease FywP)
- Comment: RR42_RS33495 from Cupriavidus basilensis FW507-4G11 (A0A0C4YP23) is the phenylalanine transporter. Ignore A2RMP5, an ortholog from another Lactococcus.
- Total: 6 characterized proteins
atoA: acetoacetyl-CoA transferase, A subunit
- Curated sequence ATOD-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &alpha. ; acetyl-CoA:acetoacetyl-CoA transferase subunit α
- Curated sequence HP0691-MONOMER: Succinyl-CoA:3-ketoacid coenzyme A transferase subunit A; Succinyl-CoA:3-oxoacid CoA-transferase; OXCT A; EC 2.8.3.5. succinyl-CoA:acetoacetate CoA-transferase subunit A (EC 2.8.3.5)
- Curated sequence GFF1045: acetyl-CoA:acetoacetate CoA transferase, A subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2111: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit A
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
atoD: acetoacetyl-CoA transferase, B subunit
- Curated sequence ATOA-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &beta. ; acetyl-CoA:acetoacetyl-CoA transferase subunit β
- Curated sequence HP0692-MONOMER: succinyl-CoA:acetoacetate CoA-transferase subunit B (EC 2.8.3.5)
- Curated sequence GFF1044: acetyl-CoA:acetoacetate CoA transferase, B subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2112: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit B
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
aacS: acetoacetyl-CoA synthetase
atoB: acetyl-CoA C-acetyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.9
- Ignore hits to items matching 2.3.1.16 when looking for 'other' hits
- Ignore hits to P07256 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (EC 2.3.1.9). Cytochrome b-c1 complex subunit 1, mitochondrial; Complex III subunit 1; Core protein I; Ubiquinol-cytochrome c oxidoreductase core protein 1; Ubiquinol-cytochrome c reductase 44 kDa protein)
- Ignore hits to I3R3D0 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to I3RA71 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to items matching similar to acetyl-CoA acetyltransferase when looking for 'other' hits
- Comment: Produces two acetyl-CoA from acetoacetyl-CoA and CoA. EC 2.3.1.16 describes a broader range of beta-ketothiolases. This enzyme is usually homomeric, but I3R3D0 and I3RA71 are non-catalytic subunits of an enzyme from Haloferax mediterranei that also contains a "normal" catalytic subunit (I3R3D1, I3RA72). Inclusion of P07256 was an error in BRENDA. And CharProtDB includes an odd annotation of the form "similar to acetyl-CoA acetyltransferase"
- Total: 36 characterized proteins
HPD: 4-hydroxyphenylpyruvate dioxygenase
- Curated proteins or TIGRFams with EC 1.13.11.27
- Ignore hits to Q8EKK9 when looking for 'other' hits (4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27))
- Ignore hits to Q9RSJ4 when looking for 'other' hits (4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27))
- Comment: Q8EKK9 and Q9RSJ4 are misannotated in BRENDA
- Total: 1 HMMs and 17 characterized proteins
hmgA: homogentisate dioxygenase
maiA: maleylacetoacetate isomerase
fahA: fumarylacetoacetate hydrolase
bcrA: ATP-dependent benzoyl-CoA reductase, alpha subunit
- Curated sequence O87876: Benzoyl-CoA reductase subunit A; 3-hydroxybenzoyl-CoA reductase subunit alpha; EC 1.3.7.8; EC 1.3.99.n1. benzoyl-CoA reductase (EC 1.3.7.8). benzoyl-CoA reductase α subunit (EC 1.3.7.8)
- Curated sequence O07462: benzoyl-CoA reductase (EC 1.3.7.8). BadF (EC 1.3.7.8)
- Curated sequence Q8VUG0: benzoyl-CoA reductase (EC 1.3.7.8)
- Ignore hits to items matching 1.3.7.8 when looking for 'other' hits
- Comment: Thauera aromatica has BrcABCD; a similar system in Rhodopseudomonas palustris is known as badFEDG; and a similar system in Azoarcus is known as BzdQONP (see PMC516837 and Genbank AF521665). [The curated entries for Azoarcus, in BRENDA, are from another strain and are not quite identical to the protein sequences in AF521665]
- Total: 3 characterized proteins
bcrB: ATP-dependent benzoyl-CoA reductase, beta subunit
- Curated sequence O87875: Benzoyl-CoA reductase subunit B; 3-hydroxybenzoyl-CoA reductase subunit beta; EC 1.3.7.8; EC 1.3.99.n1. benzoyl-CoA reductase β subunit (EC 1.3.7.8)
- Curated sequence O07461: benzoyl-CoA reductase (EC 1.3.7.8). BadE (EC 1.3.7.8)
- Curated sequence Q8VUG2: benzoyl-CoA reductase (EC 1.3.7.8)
- Ignore hits to items matching 1.3.7.8 when looking for 'other' hits
- Total: 3 characterized proteins
bcrC: ATP-dependent benzoyl-CoA reductase, gamma subunit
- Curated sequence O87874: Benzoyl-CoA reductase subunit C; 3-hydroxybenzoyl-CoA reductase subunit gamma; EC 1.3.7.8; EC 1.3.99.n1. benzoyl-CoA reductase γ subunit (EC 1.3.7.8)
- Curated sequence O07460: BadD (EC 1.3.7.8). benzoyl-CoA reductase (EC 1.3.7.8)
- Curated sequence Q8VUG3: benzoyl-CoA reductase (EC 1.3.7.8)
- Ignore hits to items matching 1.3.7.8 when looking for 'other' hits
- Total: 3 characterized proteins
bcrD: ATP-dependent benzoyl-CoA reductase, delta subunit
- Curated sequence O87877: Benzoyl-CoA reductase subunit D; 3-hydroxybenzoyl-CoA reductase subunit delta; EC 1.3.7.8; EC 1.3.99.n1. benzoyl-CoA reductase δ subunit (EC 1.3.7.8)
- Curated sequence O07463: BadG (EC 1.3.7.8). benzoyl-CoA reductase (EC 1.3.7.8)
- Curated sequence Q8VUG1: benzoyl-CoA reductase (EC 1.3.7.8)
- Ignore hits to items matching 1.3.7.8 when looking for 'other' hits
- Total: 3 characterized proteins
bamB: class II benzoyl-CoA reductase, BamB subunit
- UniProt sequence Q39TV8: SubName: Full=Benzoyl-CoA reductase, putative {ECO:0000313|EMBL:ABB32316.1};
- Comment: bamBCDEFGHI has been described in Geobacter metallireducens (PMID:30674680). There is also a paper about the enzyme from Desulfocarcina cetonica but I could not find those sequences. bamB = Gmet_2087
- Total: 1 characterized proteins
bamC: class II benzoyl-CoA reductase, BamC subunit
- UniProt sequence Q39TV9: SubName: Full=Iron-sulfur cluster-binding oxidoreductase, putative benzoyl-CoA reductase electron transfer protein {ECO:0000313|EMBL:ABB32315.1};
- Comment: bamC = Gmet_2086
- Total: 1 characterized proteins
bamD: class II benzoyl-CoA reductase, BamD subunit
- UniProt sequence Q39TW0: SubName: Full=Iron-sulfur cluster-binding oxidoreductase, CCG domain pair-containing, putative benzoyl-CoA reductase electron transfer protein {ECO:0000313|EMBL:ABB32314.1};
- Comment: bamD = Gmet_2085
- Total: 1 characterized proteins
bamE: class II benzoyl-CoA reductase, BamE subunit
- UniProt sequence Q39TW1: SubName: Full=Polyferredoxin, putative benzoyl-CoA reductase electron transfer protein {ECO:0000313|EMBL:ABB32313.1};
- Comment: bamE = Gmet_2084
- Total: 1 characterized proteins
bamF: class II benzoyl-CoA reductase, BamF subunit
- UniProt sequence Q39TW2: SubName: Full=Benzoyl-CoA reductase electron transfer protein, selenocysteine-containing, putative {ECO:0000313|EMBL:ABB32312.2};
- Comment: bamF = Gmet_2083
- Total: 1 characterized proteins
bamG: class II benzoyl-CoA reductase, BamG subunit
- UniProt sequence Q39TW4: SubName: Full=Benzoyl-CoA reductase electron transfer protein, putative {ECO:0000313|EMBL:ABB32310.1};
- Comment: bamG = Gmet_2081
- Total: 1 characterized proteins
bamH: class II benzoyl-CoA reductase, BamH subunit
- UniProt sequence Q39TW5: SubName: Full=Benzoyl-CoA reductase electron transfer protein, putative {ECO:0000313|EMBL:ABB32309.1};
- Comment: bamH = Gmet_2080
- Total: 1 characterized proteins
bamI: class II benzoyl-CoA reductase, BamI subunit
- UniProt sequence Q39TW6: SubName: Full=Iron-sulfur cluster-binding protein, putative {ECO:0000313|EMBL:ABB32308.1};
- Comment: bamI = Gmet_2079
- Total: 1 characterized proteins
gcdH: glutaryl-CoA dehydrogenase
ech: (S)-3-hydroxybutanoyl-CoA hydro-lyase
- Curated proteins or TIGRFams with EC 4.2.1.150
- Ignore hits to Q97MS7 when looking for 'other' hits (short-chain-enoyl-CoA hydratase (EC 4.2.1.150))
- Curated sequence BPHYT_RS17335: trans-2,3-dehydroadipyl-CoA hydratase (EC 4.2.1.17)
- Curated sequence GFF2389: Enoyl-CoA hydratase [valine degradation] (EC 4.2.1.17)
- Ignore hits to items matching 4.2.1.17 when looking for 'other' hits
- Comment: Psest_2437 (GFF2389) is the enoyl-CoA hydrotase for both isoleucine and valine degradation, which implies that (S)-3-hydroxybutanoyl-CoA is a substrate. Q97MS7 is misannotated in BRENDA. BPHYT_RS17335 was misannotated as paaF; it is very similar to the ech H16_A3307, which is a different explanation for its role in phenylacetate utilization. Short-chain enoyl-CoA hydratases are sometimes given EC 4.2.1.17 instead, so those are ignored.
- Total: 8 characterized proteins
fadB: (S)-3-hydroxybutanoyl-CoA dehydrogenase
- Curated proteins or TIGRFams with EC 1.1.1.35
- Ignore hits to GFF1550 when looking for 'other' hits (Enoyl-CoA hydratase (EC 4.2.1.17))
- Comment: HP15_1512 (GFF1550) is annotated as enoyl-CoA hydratase but likely does this as well
- Total: 36 characterized proteins
padB: phenylacetyl-CoA dehydrogenase, PadB subunit
- UniProt sequence A0A2R4BLL6: SubName: Full=Phenylacetyl-CoA:acceptor oxidoreductase large subunit PadB {ECO:0000313|EMBL:AVR88225.1}; EC=1.8.5.3 {ECO:0000313|EMBL:AVR88225.1};
- Comment: phenylacetyl-CoA oxidoreductase has three subunits, padBCD. The system from Thauera aromatica includes 93 kDa protein: TTPNxPtGVtKVAtY = padB = Tharo_1297 = A0A2R4BLL6; 27 kDa protein: TRYAMVADLRRxVGxQTxTAAxKHTNATPP = padC = Tharo_1296 = A0A2R4BLY8; 26 kDa protein: kRGVQPELQPFtDAr = padD = Tharo_1295 = A0A2R4BLZ0 (see N-terminal sequences in PMID:10336636). TCDB 5.A.3.11.1 / Q5P037 describes a related system, not the system from T. aromatica, and I'm not sure if those sequences are actually characterized.
- Total: 1 characterized proteins
padC: phenylacetyl-CoA dehydrogenase, PadC subunit
- UniProt sequence A0A2R4BLY8: SubName: Full=Phenylacetyl-CoA:acceptor oxidoreductase small subunit PadC {ECO:0000313|EMBL:AVR88224.1};
- Ignore hits to Q5P036 when looking for 'other' hits (Molybdenum enzyme, medium subunit,related to phenylacetyl-CoA: acceptor oxidoreductase, component of Phenylacetyl-CoA:acceptor oxidoreductase)
- Total: 1 characterized proteins
padD: phenylacetyl-CoA dehydrogenase, PadD subunit
- UniProt sequence A0A2R4BLZ0: SubName: Full=Phenylacetyl-CoA:acceptor oxidoreductase-like protein subunit C, PadD {ECO:0000313|EMBL:AVR88223.1}; EC=1.8.5.3 {ECO:0000313|EMBL:AVR88223.1};
- Ignore hits to Q5P0H8 when looking for 'other' hits (Phenylacetyl-CoA:acceptor oxidoreductase, component of Phenylacetyl-CoA:acceptor oxidoreductase)
- Total: 1 characterized proteins
padG: phenylglyoxylate dehydrogenase, alpha subunit
- Curated sequence Q8L3B1: NADH-dependent phenylglyoxylate dehydrogenase subunit alpha; Phenylglyoxylate:NAD oxidoreductase; Phenylglyoxylate:acceptor oxidoreductase; EC 1.2.1.58
- Comment: phenylglyoxylate dehydrogenase has 5 subunits, padEFGHI, in Aromatoleum evansii
- Total: 1 characterized proteins
padI: phenylglyoxylate dehydrogenase, beta subunit
- Curated sequence Q8L3A9: NADH-dependent phenylglyoxylate dehydrogenase subunit beta; Phenylglyoxylate:NAD oxidoreductase; Phenylglyoxylate:acceptor oxidoreductase; EC 1.2.1.58
- Total: 1 characterized proteins
padE: phenylglyoxylate dehydrogenase, gamma subunit
- Curated sequence Q8L3B3: NADH-dependent phenylglyoxylate dehydrogenase subunit gamma; Phenylglyoxylate:NAD oxidoreductase; Phenylglyoxylate:acceptor oxidoreductase; EC 1.2.1.58
- Total: 1 characterized proteins
padF: phenylglyoxylate dehydrogenase, delta subunit
- Curated sequence Q8L3B2: NADH-dependent phenylglyoxylate dehydrogenase subunit delta; Phenylglyoxylate:NAD oxidoreductase; Phenylglyoxylate:acceptor oxidoreductase; EC 1.2.1.58
- Total: 1 characterized proteins
padH: phenylglyoxylate dehydrogenase, epsilon subunit
- Curated sequence Q8L3B0: NADH-dependent phenylglyoxylate dehydrogenase subunit epsilon; Phenylglyoxylate:NAD oxidoreductase; Phenylglyoxylate:acceptor oxidoreductase; EC 1.2.1.58
- Total: 1 characterized proteins
dch: cyclohexa-1,5-diene-1-carboxyl-CoA hydratase
had: 6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
oah: 6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
pimB: 3-oxopimeloyl-CoA:CoA acetyltransferase
Ch1CoA: cyclohex-1-ene-1-carbonyl-CoA dehydrogenase
badK: cyclohex-1-ene-1-carboxyl-CoA hydratase
badH: 2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase
badI: 2-ketocyclohexanecarboxyl-CoA hydrolase
pimD: pimeloyl-CoA dehydrogenase, large subunit
pimC: pimeloyl-CoA dehydrogenase, small subunit
pimF: 6-carboxyhex-2-enoyl-CoA hydratase
boxA: benzoyl-CoA epoxidase, subunit A
- Curated sequence Q9AIX6: Benzoyl-CoA oxygenase component A; Benzoyl-CoA 2,3-dioxygenase subunit A; Benzoyl-CoA dioxygenase reductase component; EC 1.14.13.208. benzoyl-CoA 2,3-epoxidase (subunit 2/2) (EC 1.14.13.208). benzoyl-CoA oxygenase component A subunit
- Comment: From EC 1.14.13.208
- Total: 1 characterized proteins
boxB: benzoyl-CoA epoxidase, subunit B
- Curated sequence Q9AIX7: Benzoyl-CoA oxygenase component B; Benzoyl-CoA 2,3-dioxygenase subunit B; Benzoyl-CoA dioxygenase oxygenase component; EC 1.14.13.208. benzoyl-CoA 2,3-epoxidase (subunit 1/2) (EC 1.14.13.208). benzoyl-CoA oxygenase component B (EC 1.14.13.208)
- Total: 1 characterized proteins
boxC: 2,3-epoxybenzoyl-CoA dihydrolase
boxD: 3,4-dehydroadipyl-CoA semialdehyde dehydrogenase
- Curated proteins or TIGRFams with EC 1.2.1.77
- Ignore hits to items matching 1.2.1.91 when looking for 'other' hits
- Comment: This reaction is similar to that of 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase (EC 1.2.1.91)
- Total: 2 characterized proteins
paaK: phenylacetate-CoA ligase
paaA: phenylacetyl-CoA 1,2-epoxidase, subunit A
- Curated sequence P76077: 1,2-phenylacetyl-CoA epoxidase, subunit A; 1,2-phenylacetyl-CoA epoxidase, catalytic subunit alpha; 1,2-phenylacetyl-CoA monooxygenase, subunit A; EC 1.14.13.149. phenylacetyl-CoA 1,2-epoxidase, monooxygenase subunit (EC 1.14.13.149). phenylacetyl-CoA 1,2-epoxidase, monooxygenase subunit (EC 1.14.13.149)
- Curated sequence MONOMER-15947: ring 1,2-phenylacetyl-CoA epoxidase PaaA subunit (EC 1.14.13.149)
- Total: 2 characterized proteins
paaB: phenylacetyl-CoA 1,2-epoxidase, subunit B
- Curated sequence P76078: 1,2-phenylacetyl-CoA epoxidase, subunit B; 1,2-phenylacetyl-CoA monooxygenase, subunit B. phenylacetyl-CoA 1,2-epoxidase subunit B (EC 1.14.13.149). phenylacetyl-CoA 1,2-epoxidase subunit B (EC 1.14.13.149)
- Curated sequence MONOMER-15948: ring 1,2-phenylacetyl-CoA epoxidase PaaB subunit (EC 1.14.13.149)
- Total: 2 characterized proteins
paaC: phenylacetyl-CoA 1,2-epoxidase, subunit C
- Curated sequence P76079: phenylacetyl-CoA 1,2-epoxidase (EC 1.14.13.149). 1,2-phenylacetyl-CoA epoxidase, subunit C; 1,2-phenylacetyl-CoA epoxidase, structural subunit beta; 1,2-phenylacetyl-CoA monooxygenase, subunit C. phenylacetyl-CoA 1,2-epoxidase, structural subunit (EC 1.14.13.149). phenylacetyl-CoA 1,2-epoxidase, structural subunit (EC 1.14.13.149)
- Curated sequence MONOMER-15949: ring 1,2-phenylacetyl-CoA epoxidase PaaC subunit (EC 1.14.13.149)
- Total: 2 characterized proteins
paaE: phenylacetyl-CoA 1,2-epoxidase, subunit E
- Curated sequence P76081: 1,2-phenylacetyl-CoA epoxidase, subunit E; 1,2-phenylacetyl-CoA epoxidase, reductase subunit; 1,2-phenylacetyl-CoA monooxygenase, subunit E; EC 1.-.-.-. phenylacetyl-CoA 1,2-epoxidase, reductase subunit (EC 1.14.13.149). phenylacetyl-CoA 1,2-epoxidase, reductase subunit (EC 1.14.13.149)
- Curated sequence MONOMER-15950: ring 1,2-phenylacetyl-CoA epoxidase PaaE subunit (EC 1.14.13.149)
- Total: 2 characterized proteins
paaG: 1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase
- Curated proteins or TIGRFams with EC 5.3.3.18
- Comment: In MetaCyc, PaaG is described as a 1,2-epoxyphenylacetyl-CoA isomerase, but it is now thought to isomerize 2-(oxepinyl)acetyl-CoA to oxepin-CoA as well as cis-3,4-didehydroadiyplCoA to trans-2,3-didehydroadiypl-CoA (see PMID:31689071).
- Total: 2 characterized proteins
paaZ1: oxepin-CoA hydrolase
- Curated proteins or TIGRFams with EC 3.3.2.12
- UniProt sequence A0A2Z5MCI7: SubName: Full=Enoyl-CoA hydratase {ECO:0000313|EMBL:AXF14912.1}; EC=4.2.1.17 {ECO:0000313|EMBL:AXF14912.1};
- Comment: PaaZ is a fusion protein of hydrolase and aldehyde dehydrogenase domains. However, in many bacteria that use this pathway, the 3-oxo-5,6-didehydrosuberyl-CoA dehydrogenase is a separate protein (PMC3064157). That study identified a single-domain protein (CAI08632.1) with oxepin-CoA hydrolase activity, but it was ~1,000x more active as a crotonyl-CoA hydrolase; since we are not sure if its oxepin-CoA hydrolase activity is physiologically relevant, we did not include it. In Paraburkholderia bryophila 376MFSha3.1, which has a single-domain 3-oxo-5,6-didehydrosuberyl-CoA dehydrogenase, the putative enoyl-CoA hydrolase H281DRAFT_04594 (A0A2Z5MCI7) is very important for phenylacetate utilization, and we predict that it is the missing oxepin-CoA hydrolase. (H281DRAFT_04594 is related to enoyl-CoA hydratases that form (S)-3-hydroxylacyl-CoA, while the hydrolase domain of PaaZ is related to enoyl-CoA hydratases that form (R)-3-hydroxylacyl-CoA. In fact, PaaZ can dehydrate (R)-3-hydroxybutyryl-CoA (PMC3064157).)
- Total: 2 characterized proteins
paaZ2: 3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase
- Curated proteins or TIGRFams with EC 1.2.1.91
- UniProt sequence Q5P3J4: SubName: Full=PaaZ protein involved in aerobic phenylacetate metabolism {ECO:0000313|EMBL:CAI08120.1};
- Ignore hits to items matching 1.2.1.77 when looking for 'other' hits
- Comment: PaaZ is a fusion protein of hydrolase and aldehyde dehydrogenase domains. However, a single-domain dehydrogenase has also been characterized (PacL = CAI08120 = Q5P3J4; see PMC3064157). Some of these dehydrogenases are closely related to 3,4-dehydroadipyl-CoA semialdehyde dehydrogenases (EC 1.2.1.77), which perform a similar reaction, so similarity to those are ignored.
- Total: 3 characterized proteins
paaJ1: 3-oxo-5,6-dehydrosuberyl-CoA thiolase
- Curated proteins or TIGRFams with EC 2.3.1.223
- Ignore hits to items matching 2.3.1.174 when looking for 'other' hits
- Ignore hits to Q845J3 when looking for 'other' hits (3-oxo-5,6-didehydrosuberyl-CoA thiolase (EC 2.3.1.223))
- UniProt sequence B2SYZ2: RecName: Full=3-oxoadipyl-CoA thiolase {ECO:0000256|ARBA:ARBA00012233}; EC=2.3.1.174 {ECO:0000256|ARBA:ARBA00012233};
- UniProt sequence A0A2Z5MFE9: RecName: Full=3-oxoadipyl-CoA thiolase {ECO:0000256|ARBA:ARBA00012233}; EC=2.3.1.174 {ECO:0000256|ARBA:ARBA00012233};
- UniProt sequence D8ITH5: RecName: Full=3-oxoadipyl-CoA thiolase {ECO:0000256|ARBA:ARBA00012233}; EC=2.3.1.174 {ECO:0000256|ARBA:ARBA00012233};
- Curated sequence GFF2751: Beta-ketoadipyl CoA thiolase (EC 2.3.1.-)
- Comment: PaaJ is a thiolase with two activities that are linked to two different EC numbers, so it is listed twice, as paaJ1 and paaJ2. The product of the first thiolase reaction should be 3,4-dehydroadipyl-CoA, not 2,3-dehydro-, so there is probably a second isomerization step, which might be catalyzed by paaG or by paaJ itself. In Burkholderia phytofirmans PsJN, this enzyme is BPHYT_RS17345 (B2SYZ2). In Paraburkholderia bryophila 376MFSha3.1, it is H281DRAFT_05723 (A0A2Z5MFE9). In Herbaspirillum seropedicae, it is HSERO_RS20660 (D8ITH5). In Marinobacter adhaerens, it is HP15_2695 (GFF2751). In BRENDA, Q845J3 is misannotated as paaJ; it is probably an accessory protein for assembly of the epoxidase (paaD, not included here).
- Total: 7 characterized proteins
paaF: 2,3-dehydroadipyl-CoA hydratase
- Curated sequence P76082: enoyl-CoA hydratase (EC 4.2.1.17). 2,3-dehydroadipyl-CoA hydratase; Enoyl-CoA hydratase; EC 4.2.1.17
- Curated sequence MONOMER-15953: 2,3-dehydroadipyl-CoA hydratase (EC 4.2.1.17)
- Curated sequence BPHYT_RS17335: trans-2,3-dehydroadipyl-CoA hydratase (EC 4.2.1.17)
- UniProt sequence A0A2Z5MEB0: SubName: Full=Enoyl-CoA hydratase {ECO:0000313|EMBL:AXF15582.1};
- Comment: This reaction is associated with EC 4.2.1.17, which is very broad (enoyl-CoA hydratase). P76081 is E. coli paaF and MONOMER-15953 is the characterized enzyme from Pseudomonas sp. Y2. BPHYT_RS17335 from Burkholderia phytofirmans and H281DRAFT_05725 (A0A2Z5MEB0) from Paraburkholderia bryophila 376MFSha3.1 are required for phenylacetate utilization and are distantly related to E. coli paaF.
- Total: 4 characterized proteins
paaH: 3-hydroxyadipyl-CoA dehydrogenase
- Curated proteins or TIGRFams with EC 1.1.1.35
- Curated sequence GFF2749: 3-hydroxyacyl-CoA dehydrogenase PaaC (EC 1.1.1.-)
- Ignore hits to GFF1550 when looking for 'other' hits (Enoyl-CoA hydratase (EC 4.2.1.17))
- Comment: This step is described by 1.1.1.35, a broader term for 3-hydroxyacyl-CoA dehydrogenases. HP15_2693 (GFF2749) is involved in phenylalanine degradation via phenylacetyl-CoA and likely has this activity. HP15_1512 (GFF1550) is annotated as enoyl-CoA hydratase but likely has 3-hydroxyacyl-CoA dehydrogenase activity as well.
- Total: 37 characterized proteins
paaJ2: 3-oxoadipyl-CoA thiolase
- Curated proteins or TIGRFams with EC 2.3.1.174
- Ignore hits to items matching 2.3.1.223 when looking for 'other' hits
- UniProt sequence B2SYZ2: RecName: Full=3-oxoadipyl-CoA thiolase {ECO:0000256|ARBA:ARBA00012233}; EC=2.3.1.174 {ECO:0000256|ARBA:ARBA00012233};
- UniProt sequence A0A2Z5MFE9: RecName: Full=3-oxoadipyl-CoA thiolase {ECO:0000256|ARBA:ARBA00012233}; EC=2.3.1.174 {ECO:0000256|ARBA:ARBA00012233};
- UniProt sequence D8ITH5: RecName: Full=3-oxoadipyl-CoA thiolase {ECO:0000256|ARBA:ARBA00012233}; EC=2.3.1.174 {ECO:0000256|ARBA:ARBA00012233};
- Curated sequence GFF2751: Beta-ketoadipyl CoA thiolase (EC 2.3.1.-)
- Comment: Enzymes from B. phytofirmans and P. bryophila and H. seropedicae and M. adhaerens are included, as for paaJ1 above
- Total: 1 HMMs and 8 characterized proteins
ARO8: L-phenylalanine transaminase
- Curated proteins or TIGRFams with EC 2.6.1.1
- Curated proteins or TIGRFams with EC 2.6.1.27
- Curated proteins or TIGRFams with EC 2.6.1.57
- Ignore hits to Q845W8 when looking for 'other' hits (aspartate 4-decarboxylase (EC 4.1.1.12))
- Ignore hits to A0A060PQX5 when looking for 'other' hits (branched-chain-amino-acid transaminase (EC 2.6.1.42))
- Ignore hits to P52878 when looking for 'other' hits (Phosphoserine aminotransferase; Phosphohydroxythreonine aminotransferase; PSAT; EC 2.6.1.52. phosphoserine transaminase (EC 2.6.1.52))
- Ignore hits to O57946 when looking for 'other' hits (kynurenine-oxoglutarate transaminase (EC 2.6.1.7))
- Comment: Several pathways involve transamination to phenylpyruvate
- Total: 95 characterized proteins
ARO10: phenylpyruvate decarboxylase
PPDCalpha: phenylpyruvate decarboxylase, alpha subunit
- Curated sequence A0A222AKA3: phenylpyruvate decarboxylase (EC 4.1.1.43)
- Comment: The alpha subunit is MF179145 = A0A222AKA3 (which appears in BRENDA)
- Total: 1 characterized proteins
PPDCbeta: phenylpyruvate decarboxylase, beta subunit
- UniProt sequence G1UHX5: SubName: Full=Putative branched-chain alpha keto acid dehydrogenase E1 subunit beta {ECO:0000313|EMBL:BAK86401.1};
- Comment: The beta subunit is not curated but is MF179146 = ASO76824.1, identical in sequence to G1UHX5
- Total: 1 characterized proteins
iorA: phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
- Curated sequence O07835: indolepyruvate ferredoxin oxidoreductase (subunit 2/2) (EC 1.2.7.8)
- Curated sequence Q6LZB6: indolepyruvate ferredoxin oxidoreductase (subunit 2/2) (EC 1.2.7.8)
- Curated sequence Q6M0F5: indolepyruvate ferredoxin oxidoreductase (subunit 2/2) (EC 1.2.7.8)
- Curated sequence P80910: Indolepyruvate oxidoreductase subunit IorA; IOR; Indolepyruvate ferredoxin oxidoreductase subunit alpha; EC 1.2.7.8
- Total: 4 characterized proteins
iorB: phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
- Curated sequence O07836: indolepyruvate ferredoxin oxidoreductase (subunit 1/2) (EC 1.2.7.8)
- Curated sequence Q6LZB5: indolepyruvate ferredoxin oxidoreductase (subunit 1/2) (EC 1.2.7.8)
- Curated sequence Q6M0F6: indolepyruvate ferredoxin oxidoreductase (subunit 1/2) (EC 1.2.7.8)
- Curated sequence P80911: Indolepyruvate oxidoreductase subunit IorB; IOR; Indolepyruvate ferredoxin oxidoreductase subunit beta; EC 1.2.7.8
- Total: 4 characterized proteins
iorAB: phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB
- Curated sequence BPHYT_RS02015: phenylpyruvate ferredoxin oxidoreductase (EC 1.2.7.8)
- Curated sequence GFF880: phenylpyruvate ferredoxin oxidoreductase (EC 1.2.7.8)
- UniProt sequence I7EJ57: SubName: Full=Indolepyruvate oxidoreductase {ECO:0000313|EMBL:AFO90183.1};
- Comment: A fused enzyme is described in Phaeobacter gallaeciensis (ior1 = A9ERV7 = I7EJ57, see PMC3346364).
- Total: 3 characterized proteins
pad-dh: phenylacetaldehyde dehydrogenase
pfor: phenylacetaldeyde:ferredoxin oxidoreductase
- Curated proteins or TIGRFams with EC 1.2.7.5
- UniProt sequence Q5P143: SubName: Full=Aldehyde:ferredoxin oxidoreductase,tungsten-containing {ECO:0000313|EMBL:CAI08971.1}; EC=1.2.7.- {ECO:0000313|EMBL:CAI08971.1};
- Comment: This enzyme is ebA5005 = Q5P143. It runs in parallel with a phenylacetaldehyde dehydrogenase (PMID:24214948).
- Total: 4 characterized proteins
PAH: phenylalanine 4-monooxygenase
PCBD: pterin-4-alpha-carbinoalamine dehydratase
QDPR: 6,7-dihydropteridine reductase
- Curated proteins or TIGRFams with EC 1.5.1.34
- Curated proteins or TIGRFams with EC 1.5.1.50
- Ignore hits to P26353 when looking for 'other' hits (Flavohemoprotein; Flavohemoglobin; Hemoglobin-like protein; Nitric oxide dioxygenase; NO oxygenase; NOD; EC 1.14.12.17)
- Ignore hits to P15888 when looking for 'other' hits (nitrobenzene nitroreductase (EC 1.7.1.16))
- Ignore hits to Q01234 when looking for 'other' hits (Oxygen-insensitive NAD(P)H nitroreductase; NR; EC 1.-.-.-. nitrobenzene nitroreductase (EC 1.7.1.16))
- Comment: In Pseudomonas, the cosubstrate of PAH is (6R)-L-threo-5,6,7,8-tetrahydroneopterin, also known as tetrahydromonapterin; in Chlorobaculum tepidum, it is (6R)-L-threo-5,6,7,8-tetrahydrobiopterin. EC 1.5.1.34 describes tetrahydrobiopterin reductases, while EC 1.5.1.50 describes bacterial dihydromonapterin reductases (folM in E. coli)
- Total: 7 characterized proteins
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About GapMind
Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using
ublast (a fast alternative to protein BLAST)
against a database of manually-curated proteins (most of which are experimentally characterized) or by using
HMMer with enzyme models (usually from
TIGRFam). Ublast hits may be split across two different proteins.
A candidate for a step is "high confidence" if either:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
Other blast hits with at least 50% coverage are "low confidence."
Steps with no high- or medium-confidence candidates may be considered "gaps."
For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways.
For diverse bacteria and archaea that can utilize a carbon source, there is a complete
high-confidence catabolic pathway (including a transporter) just 38% of the time, and
there is a complete medium-confidence pathway 63% of the time.
Gaps may be due to:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).
For more information, see:
If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know
by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory