4-hydroxybenzoate catabolism in Geobacter daltonii FRC-32

Best path

pcaK, 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
pcaK	4-hydroxybenzoate transporter pcaK	GEOB_RS01110
hcl	4-hydroxybenzoyl-CoA ligase	GEOB_RS00985
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	GEOB_RS00520
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	GEOB_RS00525
bamB	class II benzoyl-CoA reductase, BamB subunit	GEOB_RS01045	GEOB_RS01125
bamC	class II benzoyl-CoA reductase, BamC subunit	GEOB_RS01050	GEOB_RS01130
bamD	class II benzoyl-CoA reductase, BamD subunit	GEOB_RS01055	GEOB_RS01135
bamE	class II benzoyl-CoA reductase, BamE subunit	GEOB_RS01060	GEOB_RS01140
bamF	class II benzoyl-CoA reductase, BamF subunit	GEOB_RS01065	GEOB_RS01145
bamG	class II benzoyl-CoA reductase, BamG subunit	GEOB_RS01070	GEOB_RS01150
bamH	class II benzoyl-CoA reductase, BamH subunit	GEOB_RS01075	GEOB_RS01155
bamI	class II benzoyl-CoA reductase, BamI subunit	GEOB_RS01080	GEOB_RS01160
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	GEOB_RS00480	GEOB_RS00800
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	GEOB_RS00475
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	GEOB_RS01040
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	GEOB_RS00490	GEOB_RS01200
gcdH	glutaryl-CoA dehydrogenase	GEOB_RS10880	GEOB_RS01170
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	GEOB_RS00800	GEOB_RS01210
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	GEOB_RS00795	GEOB_RS00835
atoB	acetyl-CoA C-acetyltransferase	GEOB_RS01200	GEOB_RS00490
Alternative steps:
ackA	acetate kinase	GEOB_RS08075	GEOB_RS09010
acs	acetyl-CoA synthetase, AMP-forming	GEOB_RS00985	GEOB_RS05815
adh	acetaldehyde dehydrogenase (not acylating)	GEOB_RS17645	GEOB_RS12935
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	GEOB_RS12960	GEOB_RS12075
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	GEOB_RS01210	GEOB_RS12040
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	GEOB_RS01210	GEOB_RS15615
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	GEOB_RS00820	GEOB_RS06780
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit
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	GEOB_RS10905	GEOB_RS10900
fcbT1	tripartite 4-hydroxybenzoate transporter, substrate-binding component FcbT1
fcbT2	tripartite 4-hydroxybenzoate transporter, small DctQ-like component FcbT2
fcbT3	tripartite 4-hydroxybenzoate transporter, large permease subunit FcbT3	GEOB_RS00965
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	GEOB_RS07485
paaF	2,3-dehydroadipyl-CoA hydratase	GEOB_RS01210	GEOB_RS15615
paaH	3-hydroxyadipyl-CoA dehydrogenase	GEOB_RS00795	GEOB_RS00835
paaJ2	3-oxoadipyl-CoA thiolase	GEOB_RS00490	GEOB_RS01200
pcaB	3-carboxymuconate cycloisomerase	GEOB_RS14350
pcaC	4-carboxymuconolactone decarboxylase	GEOB_RS06910
pcaD	3-oxoadipate enol-lactone hydrolase	GEOB_RS06910
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	GEOB_RS00490	GEOB_RS01200
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)
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	GEOB_RS17645	GEOB_RS12935
praC	2-hydroxymuconate tautomerase
praD	2-oxohex-3-enedioate decarboxylase
pta	phosphate acetyltransferase	GEOB_RS08080	GEOB_RS01185
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 Sep 24 2021. The underlying query database was built on Sep 17 2021.