4-hydroxybenzoate catabolism in Desulfatiglans anilini DSM 4660

Best path

fcbT1, fcbT2, fcbT3, hcl, hcrA, hcrB, hcrC, bamB, bamC, bamD, bamE, bamF, bamG, bamH, bamI, dch, had, oah, pimB, gcdH, ech, fadB, atoB

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

72 steps (39 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
fcbT1	tripartite 4-hydroxybenzoate transporter, substrate-binding component FcbT1	H567_RS0113405
fcbT2	tripartite 4-hydroxybenzoate transporter, small DctQ-like component FcbT2
fcbT3	tripartite 4-hydroxybenzoate transporter, large permease subunit FcbT3	H567_RS0113395	H567_RS0115490
hcl	4-hydroxybenzoyl-CoA ligase	H567_RS0117150	H567_RS0120080
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	H567_RS0110270	H567_RS0113415
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit	H567_RS0121790	H567_RS0120050
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	H567_RS0110275	H567_RS0120045
bamB	class II benzoyl-CoA reductase, BamB subunit	H567_RS0102020	H567_RS0121100
bamC	class II benzoyl-CoA reductase, BamC subunit	H567_RS0102025	H567_RS23815
bamD	class II benzoyl-CoA reductase, BamD subunit	H567_RS0120870	H567_RS0108265
bamE	class II benzoyl-CoA reductase, BamE subunit	H567_RS0120855	H567_RS0108270
bamF	class II benzoyl-CoA reductase, BamF subunit	H567_RS0120850	H567_RS29250
bamG	class II benzoyl-CoA reductase, BamG subunit	H567_RS0103085	H567_RS0110430
bamH	class II benzoyl-CoA reductase, BamH subunit	H567_RS0102625	H567_RS0103080
bamI	class II benzoyl-CoA reductase, BamI subunit	H567_RS0120685	H567_RS26855
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	H567_RS0106025	H567_RS0110895
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	H567_RS0106015
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	H567_RS0106020
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	H567_RS0110730	H567_RS0115465
gcdH	glutaryl-CoA dehydrogenase	H567_RS0110890	H567_RS0117975
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	H567_RS0110895	H567_RS0118000
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	H567_RS0110735	H567_RS0107440
atoB	acetyl-CoA C-acetyltransferase	H567_RS0110910	H567_RS0110905
Alternative steps:
ackA	acetate kinase
acs	acetyl-CoA synthetase, AMP-forming	H567_RS0109385	H567_RS0111520
adh	acetaldehyde dehydrogenase (not acylating)	H567_RS0113835
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	H567_RS0117980	H567_RS0117055
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	H567_RS0114955	H567_RS0110895
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	H567_RS0110895	H567_RS0120240
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	H567_RS0113105	H567_RS0112245
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit	H567_RS0113110
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	H567_RS0113105	H567_RS0112245
boxA	benzoyl-CoA epoxidase, subunit A
boxB	benzoyl-CoA epoxidase, subunit B
boxC	2,3-epoxybenzoyl-CoA dihydrolase
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase
catI	3-oxoadipate CoA-transferase subunit A (CatI)
catJ	3-oxoadipate CoA-transferase subunit B (CatJ)
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	H567_RS0117635	H567_RS0110890
ligA	protocatechuate 4,5-dioxygenase, alpha subunit
ligB	protocatechuate 4,5-dioxygenase, beta subunit
ligC	2-hydroxy-4-carboxymuconate-6-semialdehyde dehydrogenase
ligI	2-pyrone-4,6-dicarboxylate hydrolase
ligJ	4-carboxy-2-hydroxymuconate hydratase
ligK	4-oxalocitramalate aldolase
ligU	4-oxalomesaconate tautomerase
mhpD	2-hydroxypentadienoate hydratase
mhpE	4-hydroxy-2-oxovalerate aldolase
paaF	2,3-dehydroadipyl-CoA hydratase	H567_RS0110895	H567_RS0115475
paaH	3-hydroxyadipyl-CoA dehydrogenase	H567_RS0110735	H567_RS0107440
paaJ2	3-oxoadipyl-CoA thiolase	H567_RS0110065	H567_RS0115465
pcaB	3-carboxymuconate cycloisomerase	H567_RS0115140
pcaC	4-carboxymuconolactone decarboxylase	H567_RS0103430
pcaD	3-oxoadipate enol-lactone hydrolase	H567_RS0103430
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	H567_RS0110065	H567_RS0115465
pcaG	protocatechuate 3,4-dioxygenase, beta subunit
pcaH	protocatechuate 3,4-dioxygenase, alpha subunit
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)
pcaK	4-hydroxybenzoate transporter pcaK
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit
pimF	6-carboxyhex-2-enoyl-CoA hydratase
pobA	4-hydroxybenzoate 3-monooxygenase
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase
praC	2-hydroxymuconate tautomerase
praD	2-oxohex-3-enedioate decarboxylase
pta	phosphate acetyltransferase	H567_RS29805
xylF	2-hydroxymuconate semialdehyde hydrolase

Confidence: high confidence medium confidence low confidence
transporter – transporters and PTS systems are shaded because predicting their specificity is particularly challenging.

This GapMind analysis is from Apr 09 2024. The underlying query database was built on Sep 17 2021.