Definition of phenylacetate catabolism
As rules and steps, or see full text
Rules
Overview: Phenylacetate utilization in GapMind is based on MetaCyc pathway phenylacetate degradation I (aerobic via phenylacetyl-CoA dehydrogenase, link) and pathway II (anaerobic via benzoyl-CoA, link).
- all: phenylacetate-transport and phenylacetate-degradation
- phenylacetate-degradation: paaK and phenylacetyl-CoA-degradation
- Comment: Phenylacetate is activated to phenylacetyl-CoA by paaK
- 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.
- 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).
- 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.
- phenylacetyl-CoA-dehydrogenase: padB, padC and padD
- phenylglyoxylate-dehydrogenase: padG, padI, padE, padF and padH
- phenylacetate-transport:
Steps
paaT: phenylacetate transporter Paa
- Curated sequence B6H9Q3: Peroxysomal phenylacetate/phenoxyacetate transporter, PaaT (CefT) of 564 aas
- Curated sequence Q8NKG7: CefT confers phenylacetate resistance
- Ignore hits to B6HIC2 when looking for 'other' hits (The PaaT (PenT) exporter)
- Comment: TCDB::B6HIC2 may be a phenylacetate transporter, so it is ignored
- Total: 2 characterized proteins
ppa: phenylacetate permease ppa
H281DRAFT_04042: phenylacetate:H+ symporter
- UniProt sequence A0A2Z5MFR8: SubName: Full=Aromatic amino acid transporter AroP {ECO:0000313|EMBL:AXF16205.1};
- Comment: In Paraburkholderia bryophila 376MFSha3.1, H281DRAFT_04042 is specifically important for phenylacetate utilization. It is similar to E. coli aroP, a proton symporter for aromatic amino acids
- 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
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
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
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
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
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
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
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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 the paper from 2019 on GapMind for amino acid biosynthesis, the paper from 2022 on GapMind for carbon sources, or view the source code.
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