Definition of 4-hydroxybenzoate catabolism
As rules and steps, or see full text
Rules
Overview: 4-hydroxybenzoate catabolism in GapMind is based on aerobic oxidation to 3,4-hydroxybenzoate (protocatechuate), followed by meta, ortho, or para cleavage; or reduction to benzoyl-CoA (part of a MetaCyc pathway for phenol degradation, link)
- all:
- 4-hydroxybenzoate-transport, pobA and protocatechuate-degradation
- or 4-hydroxybenzoate-transport, hcl, hcrA, hcrB, hcrC and benzoyl-CoA-degradation
- Comment: An aerobic route for degradation of 4-hydroxybenzoate involves 4-hydroxybenzoate 3-monooxygenase pobA, which forms protocatechuate (3,4-dihydroxybenzoate). Alternatively, 4-hydroxybenzoate can be activated to 4-hydroxybenzoyl-CoA by hcl and reduced to benzoyl-CoA by hcrABC (link).
- protocatechuate-degradation:
- ligA, ligB, ligC, ligI, ligU, ligJ and ligK
- or pcaH, pcaG, pcaB, pcaC, pcaD and 3-oxoadipate-degradation
- or praA and 2-hydroxymuconate-6-semialdehyde-degradation
- Comment: In the meta-cleavage pathway (link), the 4,5-dioxygenase ligAB splits protocatechuate to 4-carboxy-2-hydroxymuconate-6-semialdehyde. (In solution, this is in the hemiacetal form.) The semialdehyde is oxidized to 2-pyrone-4,6-dicarboxylate, hydrolyzed to (1E)-4-oxobut-1-ene-1,2,4-tricarboxylate, tautomerized to (1E,3E)-4-hydroxybuta-1,3-diene-1,2,4-tricarboxylate, hydrated to 2-hydroxy-4-oxobutane-1,2,4-tricarboxylate (4-oxalocitramalate), and split by an aldolase to pyruvate and oxaloacetate. In the ortho-cleavage pathway (link), the 3,4-oxygenase pcaHG cleaves the ring to 3-carboxy-cis,cis-muconate, a cycloisomerase forms 4-carboxymuconolactone (2-carboxy-2,5-dihydro-5-oxofuran-2-yl)-acetate), a decarboxylase forms 3-oxoadipate enol lactone ((4,5-dihydro-5-oxofuran-2-yl)-acetate), and a hydrolase forms 3-oxoadipate. In the para-cleavage pathway (link), the 2,3-dioxygenase praA forms (2Z,4Z)-2-hydroxy-5-carboxymuconate-6-semialdehyde, which spontaneously decarboxylates to (2Z,4E)-2-hydroxy-6-oxohexa-2,4-dienoate, also known as 2-hydroxymuconate 6-semialdehyde.
- 2-hydroxymuconate-6-semialdehyde-degradation:
- praB, praC, praD and 2-hydroxypenta-2,4-dienoate-degradation
- or xylF and 2-hydroxypenta-2,4-dienoate-degradation
- Comment: Dehydrogenase praB forms 2-hydroxymuconate, tautomerase praC forms (3E)-2-oxohex-3-enedioate (2-oxalocrotonate), and decarboxylase praD yields 2-hydroxypenta-2,4-dienoate (HPD). (This series of steps is part of protocatechuate para-cleavage, link, or catechol degradation II, link.) Or, hydrolase xylF forms HPD and formate. (This is part of a MetaCyc pathway for catechol degradation, link.)
- 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.
- 2-hydroxypenta-2,4-dienoate-degradation: mhpD, mhpE and acetaldehyde-degradation
- Comment: (2Z)-2-hydroxypenta-2,4-dienoate (HPD) is a common intermediate in the aerobic degradation of many aromatic compounds. In MetaCyc pathway 2-hydroxypenta-2,4-dienoate degradation (link), HPD is hydrated to (S)-4-hydroxy-2-oxopentanoate and an aldolase cleaves it to pyruvate and acetaldehyde.
- acetaldehyde-degradation:
- ald-dh-CoA
- or adh and acs
- or adh, ackA and pta
- Comment: Acetaldehyde can be oxidized to acetyl-CoA, or oxidized to acetate and activated to acetyl-CoA by either acetyl-CoA synthetase (acs) or by acetate kinase (ackA) and phosphate acetyltransferase (pta).
- 3-oxoadipate-degradation: 3-oxodipate-CoA-transferase and pcaF
- Comment: MetaCyc pathway 3-oxoadipate degradation (link) involves activation by CoA (using succinyl-CoA) and a thiolase (succinyltransferase) reaction that splits it to acetyl-CoA and succinyl-CoA.
- 3-oxodipate-CoA-transferase:
- pcaI and pcaJ
- or catI and catJ
- Comment: Two different types of 3-oxoadipate CoA-transferases (EC 2.8.3.6) are known. They are both heteromeric with each subunit containing a CoA-transferase domain
- 4-hydroxybenzoate-transport:
- pcaK
- or fcbT1, fcbT2 and fcbT3
- Comment: Transporters were identified using: query: transporter:4-hydroxybenzoate:p-hydroxybenzoate:4-hydroxybenzoic acid:p-hydroxybenzoic acid
Steps
pcaK: 4-hydroxybenzoate transporter pcaK
- Curated sequence Q43975: 4-hydroxybenzoate transporter PcaK; 4-HB transporter
- Curated sequence Q51955: 4-hydroxybenzoate transporter PcaK. 4-Hydroxybenzoate/protocatechuate porter
- Total: 2 characterized proteins
fcbT1: tripartite 4-hydroxybenzoate transporter, substrate-binding component FcbT1
- Curated sequence Q9RBR1: FcbT1, component of Tripartite 4-chlorobenzoate symporter (also binds and may transport 4-bromo-, 4-iodo-, and 4-fluorobenzoate and with a lower affinity, 3-chlorobenzoate, 2-chlorobenzoate, 4-hydroxybenzoate, 3-hydroxybenzoate, and benzoate)
- Comment: The primary substrate for this system is 4-chlorobenzoate, but TCDB reports that binding of that substrate to fcbT1 is inhibited by 1 mM 4-hydroxybenzoate, suggesting a reasonable affinity for 4-hydroxybenzoate as well.
- Total: 1 characterized proteins
fcbT2: tripartite 4-hydroxybenzoate transporter, small DctQ-like component FcbT2
- Curated sequence Q9RBR0: FcbT2, component of Tripartite 4-chlorobenzoate symporter (also binds and may transport 4-bromo-, 4-iodo-, and 4-fluorobenzoate and with a lower affinity, 3-chlorobenzoate, 2-chlorobenzoate, 4-hydroxybenzoate, 3-hydroxybenzoate, and benzoate)
- Total: 1 characterized proteins
fcbT3: tripartite 4-hydroxybenzoate transporter, large permease subunit FcbT3
- Curated sequence Q9RBQ9: FcbT3, component of Tripartite 4-chlorobenzoate symporter (also binds and may transport 4-bromo-, 4-iodo-, and 4-fluorobenzoate and with a lower affinity, 3-chlorobenzoate, 2-chlorobenzoate, 4-hydroxybenzoate, 3-hydroxybenzoate, and benzoate)
- Total: 1 characterized proteins
pcaI: 3-oxoadipate CoA-transferase subunit A (PcaI)
- Curated sequence CH_021928: 3-oxoadipate CoA-transferase subunit A; EC 2.8.3.6. 3-oxoadipate CoA-transferase (subunit 2/2) (EC 2.8.3.6). α subunit of β-ketoadipate succinyl-CoA transferase (EC 2.8.3.6)
- Ignore hits to items matching 2.8.3.6 when looking for 'other' hits
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Comment: Ignore EC 2.8.3.5, 3-oxoacid CoA-transferase, usually active on shorter substrates but who knows?
- Total: 1 characterized proteins
pcaJ: 3-oxoadipate CoA-transferase subunit B (PcaJ)
- Curated sequence P0A102: 3-oxoadipate CoA-transferase (subunit 1/2) (EC 2.8.3.6). 3-oxoadipate CoA-transferase subunit B; EC 2.8.3.6. β subunit of β-ketoadipate succinyl-CoA transferase (EC 2.8.3.6)
- Ignore hits to items matching 2.8.3.6 when looking for 'other' hits
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 1 characterized proteins
catI: 3-oxoadipate CoA-transferase subunit A (CatI)
- Curated sequence Q8VPF3: 3-oxoadipate CoA-transferase subunit A; 3-oxoadipate:succinyl-CoA transferase subunit A; Beta-ketoadipate:succinyl-CoA transferase subunit A; EC 2.8.3.6. 3-oxoadipate CoA-transferase (subunit 2/2) (EC 2.8.3.6)
- Curated sequence GFF1318: 3-oxoadipate CoA-transferase (EC 2.8.3.6)
- Curated sequence PfGW456L13_4592: 3-oxoadipate CoA-transferase (EC 2.8.3.6)
- Curated sequence AO353_17195: 3-oxoadipate CoA-transferase (EC 2.8.3.6)
- Ignore hits to items matching 2.8.3.6 when looking for 'other' hits
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Comment: Ignore EC 2.8.3.5, 3-oxoacid CoA-transferase, usually active on shorter substrates but who knows?
- Total: 4 characterized proteins
catJ: 3-oxoadipate CoA-transferase subunit B (CatJ)
- Curated sequence Q8VPF2: 3-oxoadipate CoA-transferase subunit B; 3-oxoadipate:succinyl-CoA transferase subunit B; Beta-ketoadipate:succinyl-CoA transferase subunit B; EC 2.8.3.6. 3-oxoadipate CoA-transferase (subunit 1/2) (EC 2.8.3.6)
- Curated sequence GFF1319: 3-oxoadipate CoA-transferase (EC 2.8.3.6)
- Curated sequence PfGW456L13_4591: 3-oxoadipate CoA-transferase (EC 2.8.3.6)
- Curated sequence AO353_17200: 3-oxoadipate CoA-transferase (EC 2.8.3.6)
- Ignore hits to items matching 2.8.3.6 when looking for 'other' hits
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
pcaF: succinyl-CoA:acetyl-CoA C-succinyltransferase
mhpD: 2-hydroxypentadienoate hydratase
mhpE: 4-hydroxy-2-oxovalerate aldolase
ald-dh-CoA: acetaldehyde dehydrogenase, acylating
- Curated proteins or TIGRFams with EC 1.2.1.10
- Ignore hits to items matching 1.1.1.1 when looking for 'other' hits
- Ignore hits to items matching 1.1.1.71 when looking for 'other' hits
- Ignore hits to items matching 1.2.1.57 when looking for 'other' hits
- Ignore hits to Q2XQZ7 when looking for 'other' hits (4-hydroxy-2-oxovalerate aldolase (EC 4.1.3.39))
- Comment: Many enzymes are multifunctional alcohol/acetaldehyde dehydrogenases, and many close homologs have just one annotation. EC 1.2.1.57 is acylating butanal dehydrogenase, which may also act on acetaldehyde. Q2XQZ7 is probably misannotated.
- Total: 2 HMMs and 20 characterized proteins
adh: acetaldehyde dehydrogenase (not acylating)
acs: acetyl-CoA synthetase, AMP-forming
ackA: acetate kinase
pta: phosphate acetyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.8
- Ignore hits to P32796 when looking for 'other' hits (carnitine O-acetyltransferase (EC 2.3.1.7); phosphate acetyltransferase (EC 2.3.1.8). Carnitine O-acetyltransferase, mitochondrial; Carnitine acetylase; EC 2.3.1.7)
- Comment: BRENDA misannotates yeast's carnitine acetyltransferase with EC 2.3.1.8
- Total: 1 HMMs and 18 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
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
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
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
pobA: 4-hydroxybenzoate 3-monooxygenase
ligA: protocatechuate 4,5-dioxygenase, alpha subunit
- Curated sequence MONOMER-15116: protocatechuate 4,5-dioxygenase alpha chain (EC 1.13.11.8). protocatechuate 4,5-dioxygenase (subunit 2/2) (EC 1.13.11.8)
- Curated sequence MONOMER-3165: protocatechuate 4,5-dioxygenase α subunit (EC 1.13.11.8; EC 1.13.11.57). protocatechuate 4,5-dioxygenase (EC 1.13.11.8)
- Ignore hits to items matching 1.13.11.8 when looking for 'other' hits
- Total: 2 characterized proteins
ligB: protocatechuate 4,5-dioxygenase, beta subunit
- Curated sequence G2IQQ3: protocatechuate 4,5-dioxygenase (subunit 1/2) (EC 1.13.11.8)
- Curated sequence MONOMER-15117: protocatechuate 4,5-dioxygenase beta chain (EC 1.13.11.8)
- Curated sequence MONOMER-3166: protocatechuate 4,5-dioxygenase β subunit (EC 1.13.11.8; EC 1.13.11.57)
- Ignore hits to items matching 1.13.11.8 when looking for 'other' hits
- Total: 3 characterized proteins
ligC: 2-hydroxy-4-carboxymuconate-6-semialdehyde dehydrogenase
ligI: 2-pyrone-4,6-dicarboxylate hydrolase
ligU: 4-oxalomesaconate tautomerase
- Curated proteins or TIGRFams with EC 5.3.2.8
- Curated sequence Q0KJL4: (4E)-oxalomesaconate Delta-isomerase; OMA isomerase; 1,3-allylic isomerase LigU; EC 5.3.3.-
- Comment: This isomerization can occur spontaneously, but the enzyme is probably required for good growth (i.e., fitness data for utilization of 4-vinylphenol or gallic acid). This enzyme is named gllD in MetaCyc. Note that ligU = Q0KJL4 is reported to carry out a different isomerization of 4-oxalomesaconate as part of this pathway. I believe this is just a question of whether to treat the product as the enol form (in UniProt) or the keto form (in MetaCyc).
- Total: 2 characterized proteins
ligJ: 4-carboxy-2-hydroxymuconate hydratase
- Curated proteins or TIGRFams with EC 4.2.1.83
- Curated sequence G2IQQ5: 2-keto-4-carboxy-3-hexenedioate hydratase; KCH hydratase; EC 4.2.1.-
- Comment: SwissProt G2IQQ5 = ligJ is described as using the enol form, (3Z)-2-oxo-4-carboxy-3-hexenedioate, of the substrate, but it yields the same product
- Total: 4 characterized proteins
ligK: 4-oxalocitramalate aldolase
praB: 2-hydroxymuconate 6-semialdehyde dehydrogenase
- Curated proteins or TIGRFams with EC 1.2.1.85
- Curated proteins or TIGRFams with EC 1.2.1.32
- Comment: EC 1.2.1.32 is 2-aminomuconate 6-semialdehyde dehydrogenase, but it is also reported to act on 2-hydroxymuconate-6-semialdehyde; many of these proteins are very similar to EC 1.2.1.85
- Total: 10 characterized proteins
praC: 2-hydroxymuconate tautomerase
praD: 2-oxohex-3-enedioate decarboxylase
xylF: 2-hydroxymuconate semialdehyde hydrolase
pcaH: protocatechuate 3,4-dioxygenase, alpha subunit
- Curated sequence A0A193DXA9: protocatechuate 3,4-dioxygenase (subunit 2/2) (EC 1.13.11.3)
- Curated sequence A8I4B7: protocatechuate 3,4-dioxygenase (EC 1.13.11.3)
- Curated sequence I0DHJ0: protocatechuate 3,4-dioxygenase (subunit 2/2) (EC 1.13.11.3)
- Curated sequence Q0SH26: protocatechuate 3,4-dioxygenase (subunit 1/2) (EC 1.13.11.3)
- Curated sequence CH_121294: protocatechuate 3,4-dioxygenase, alpha chain; EC 1.13.11.3
- Curated sequence MONOMER-14209: protocatechuate 3,4-dioxygenase type II α subunit (EC 1.13.11.3)
- Curated sequence MONOMER-3186: protocatechuate 3,4-dioxygenase α subunit (EC 1.13.11.3)
- Ignore hits to items matching 1.13.11.3 when looking for 'other' hits
- Total: 7 characterized proteins
pcaG: protocatechuate 3,4-dioxygenase, beta subunit
- Curated sequence A0A193DXP2: protocatechuate 3,4-dioxygenase (subunit 1/2) (EC 1.13.11.3)
- Curated sequence A8I4B3: protocatechuate 3,4-dioxygenase (EC 1.13.11.3)
- Curated sequence I0DHJ1: protocatechuate 3,4-dioxygenase (subunit 1/2) (EC 1.13.11.3)
- Curated sequence Q0SH27: protocatechuate 3,4-dioxygenase (subunit 2/2) (EC 1.13.11.3)
- Curated sequence CH_121290: protocatechuate 3,4-dioxygenase, beta chain; EC 1.13.11.3
- Curated sequence MONOMER-14210: protocatechuate 3,4-dioxygenase type II β subunit (EC 1.13.11.3)
- Curated sequence MONOMER-3185: protocatechuate 3,4-dioxygenase β subunit (EC 1.13.11.3)
- Ignore hits to items matching 1.13.11.3 when looking for 'other' hits
- Total: 7 characterized proteins
pcaB: 3-carboxymuconate cycloisomerase
- Curated proteins or TIGRFams with EC 5.5.1.2
- UniProt sequence A0A0C4YE08: SubName: Full=3-carboxy-cis,cis-muconate cycloisomerase {ECO:0000313|EMBL:AJG23937.1}; EC=5.5.1.2 {ECO:0000313|EMBL:AJG23937.1};
- Comment: RR42_RS32055 (A0A0C4YE08) is a somewhat diverged pcaB, confirmed by fitness data
- Total: 1 HMMs and 3 characterized proteins
pcaC: 4-carboxymuconolactone decarboxylase
pcaD: 3-oxoadipate enol-lactone hydrolase
praA: protocatechuate 2,3-dioxygenase
hcl: 4-hydroxybenzoyl-CoA ligase
- Curated proteins or TIGRFams with EC 6.2.1.27
- Curated sequence Q8GQN9: Benzoate--CoA ligase; Benzoyl-CoA synthetase; EC 6.2.1.25. benzoate-CoA ligase (EC 6.2.1.25). benzoate-CoA ligase (EC 6.2.1.32; EC 6.2.1.25)
- Ignore hits to items matching 6.2.1.25 when looking for 'other' hits
- Ignore hits to Q8VUF1 when looking for 'other' hits (benzoyl-CoA reductase (EC 1.3.7.8))
- Comment: benzoyl-CoA ligases (EC 6.2.1.25) may have this activity as well, i.e. see PMID:12897012 (discussing Q8GQN9). Q8VUF1 (probably a benzoyl-CoA ligase) is misannotated in BRENDA as benzoyl-CoA reductase.
- Total: 4 characterized proteins
hcrA: 4-hydroxybenzoyl-CoA reductase, alpha subunit
- Curated sequence O33819: 4-hydroxybenzoyl-CoA reductase subunit alpha; 4-HBCR subunit alpha; EC 1.3.7.9. 4-hydroxybenzoyl-CoA reductase α subunit (EC 1.3.7.9)
- Curated sequence MONOMER-14376: 4-hydroxybenzoyl-CoA reductase, α subunit (EC 1.3.7.9)
- Curated sequence MONOMER-17404: 4-hydroxybenzoyl-CoA reductase HbaC subunit (EC 1.3.7.9)
- Ignore hits to items matching 1.1.7.1 when looking for 'other' hits
- Ignore hits to items matching 1.3.7.9 when looking for 'other' hits
- Comment: EC 1.3.7.9 has been transferred to EC 1.1.7.1, but currently the annotations still use 1.3.7.9
- Total: 3 characterized proteins
hcrB: 4-hydroxybenzoyl-CoA reductase, beta subunit
- Curated sequence O33820: 4-hydroxybenzoyl-CoA reductase subunit beta; 4-HBCR subunit beta; EC 1.3.7.9. 4-hydroxybenzoyl-CoA reductase β subunit (EC 1.3.7.9)
- Curated sequence MONOMER-14377: 4-hydroxybenzoyl-CoA reductase, β subunit (EC 1.3.7.9)
- Curated sequence MONOMER-17405: 4-hydroxybenzoyl-CoA reductase HbaD subunit (EC 1.3.7.9)
- Ignore hits to items matching 1.1.7.1 when looking for 'other' hits
- Ignore hits to items matching 1.3.7.9 when looking for 'other' hits
- Total: 3 characterized proteins
hcrC: 4-hydroxybenzoyl-CoA reductase, gamma subunit
- Curated sequence O33818: 4-hydroxybenzoyl-CoA reductase subunit gamma; 4-HBCR subunit gamma; EC 1.3.7.9. 4-hydroxybenzoyl-CoA reductase γ subunit (EC 1.3.7.9)
- Curated sequence MONOMER-14378: 4-hydroxybenzoyl-CoA reductase, γ subunit (EC 1.3.7.9)
- Curated sequence MONOMER-17403: 4-hydroxybenzoyl-CoA reductase HbaB subunit (EC 1.3.7.9)
- Ignore hits to items matching 1.1.7.1 when looking for 'other' hits
- Ignore hits to items matching 1.3.7.9 when looking for 'other' hits
- Total: 3 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