4-hydroxybenzoate catabolism in Azoarcus sp. BH72

Best path

pcaK, pobA, ligA, ligB, ligC, ligI, ligU, ligJ, ligK

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 (47 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
pcaK	4-hydroxybenzoate transporter pcaK	AZO_RS12820
pobA	4-hydroxybenzoate 3-monooxygenase	AZO_RS12350
ligA	protocatechuate 4,5-dioxygenase, alpha subunit	AZO_RS12795	AZO_RS12720
ligB	protocatechuate 4,5-dioxygenase, beta subunit	AZO_RS12790	AZO_RS12715
ligC	2-hydroxy-4-carboxymuconate-6-semialdehyde dehydrogenase	AZO_RS12785
ligI	2-pyrone-4,6-dicarboxylate hydrolase	AZO_RS12800
ligU	4-oxalomesaconate tautomerase	AZO_RS12825
ligJ	4-carboxy-2-hydroxymuconate hydratase	AZO_RS12815
ligK	4-oxalocitramalate aldolase	AZO_RS12810	AZO_RS05740
Alternative steps:
ackA	acetate kinase	AZO_RS06410	AZO_RS18270
acs	acetyl-CoA synthetase, AMP-forming	AZO_RS12180	AZO_RS08590
adh	acetaldehyde dehydrogenase (not acylating)	AZO_RS14770	AZO_RS10715
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	AZO_RS12270	AZO_RS09390
atoB	acetyl-CoA C-acetyltransferase	AZO_RS01980	AZO_RS10980
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	AZO_RS19640	AZO_RS05160
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	AZO_RS03985	AZO_RS08595
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	AZO_RS03985	AZO_RS09740
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit
bamE	class II benzoyl-CoA reductase, BamE subunit
bamF	class II benzoyl-CoA reductase, BamF subunit
bamG	class II benzoyl-CoA reductase, BamG subunit
bamH	class II benzoyl-CoA reductase, BamH subunit	AZO_RS07090	AZO_RS07145
bamI	class II benzoyl-CoA reductase, BamI subunit	AZO_RS15255	AZO_RS07095
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit
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	AZO_RS15360
boxB	benzoyl-CoA epoxidase, subunit B	AZO_RS15355
boxC	2,3-epoxybenzoyl-CoA dihydrolase	AZO_RS15350
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	AZO_RS15340
catI	3-oxoadipate CoA-transferase subunit A (CatI)
catJ	3-oxoadipate CoA-transferase subunit B (CatJ)
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	AZO_RS01985	AZO_RS15455
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	AZO_RS09740	AZO_RS15415
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	AZO_RS03985	AZO_RS09740
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	AZO_RS02360	AZO_RS05220
fcbT1	tripartite 4-hydroxybenzoate transporter, substrate-binding component FcbT1	AZO_RS11530
fcbT2	tripartite 4-hydroxybenzoate transporter, small DctQ-like component FcbT2	AZO_RS11540
fcbT3	tripartite 4-hydroxybenzoate transporter, large permease subunit FcbT3	AZO_RS11535	AZO_RS04640
gcdH	glutaryl-CoA dehydrogenase	AZO_RS09725	AZO_RS09755
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hcl	4-hydroxybenzoyl-CoA ligase	AZO_RS15330	AZO_RS10080
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	AZO_RS00105	AZO_RS11170
mhpD	2-hydroxypentadienoate hydratase	AZO_RS09375	AZO_RS12280
mhpE	4-hydroxy-2-oxovalerate aldolase	AZO_RS09395	AZO_RS12265
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
paaF	2,3-dehydroadipyl-CoA hydratase	AZO_RS03985	AZO_RS09740
paaH	3-hydroxyadipyl-CoA dehydrogenase	AZO_RS02360	AZO_RS15265
paaJ2	3-oxoadipyl-CoA thiolase	AZO_RS15365	AZO_RS01570
pcaB	3-carboxymuconate cycloisomerase
pcaC	4-carboxymuconolactone decarboxylase	AZO_RS19855
pcaD	3-oxoadipate enol-lactone hydrolase
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	AZO_RS15365	AZO_RS01570
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)
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	AZO_RS02365	AZO_RS01570
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit
pimF	6-carboxyhex-2-enoyl-CoA hydratase	AZO_RS02345
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	AZO_RS12285	AZO_RS09370
praC	2-hydroxymuconate tautomerase	AZO_RS12255	AZO_RS09385
praD	2-oxohex-3-enedioate decarboxylase	AZO_RS12260	AZO_RS09380
pta	phosphate acetyltransferase	AZO_RS18265	AZO_RS16135
xylF	2-hydroxymuconate semialdehyde hydrolase	AZO_RS09945	AZO_RS09890

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.