4-hydroxybenzoate catabolism in Paraburkholderia phymatum STM815

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 (54 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
pcaK	4-hydroxybenzoate transporter pcaK	BPHY_RS20200	BPHY_RS30475
pobA	4-hydroxybenzoate 3-monooxygenase	BPHY_RS31765	BPHY_RS20225
ligA	protocatechuate 4,5-dioxygenase, alpha subunit	BPHY_RS16285
ligB	protocatechuate 4,5-dioxygenase, beta subunit	BPHY_RS16280	BPHY_RS31735
ligC	2-hydroxy-4-carboxymuconate-6-semialdehyde dehydrogenase	BPHY_RS16275
ligI	2-pyrone-4,6-dicarboxylate hydrolase	BPHY_RS16290	BPHY_RS34750
ligU	4-oxalomesaconate tautomerase	BPHY_RS16305	BPHY_RS33400
ligJ	4-carboxy-2-hydroxymuconate hydratase	BPHY_RS31725	BPHY_RS16300
ligK	4-oxalocitramalate aldolase	BPHY_RS31720	BPHY_RS16295
Alternative steps:
ackA	acetate kinase	BPHY_RS18625	BPHY_RS10635
acs	acetyl-CoA synthetase, AMP-forming	BPHY_RS09860	BPHY_RS34900
adh	acetaldehyde dehydrogenase (not acylating)	BPHY_RS23385	BPHY_RS00050
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	BPHY_RS17785	BPHY_RS22820
atoB	acetyl-CoA C-acetyltransferase	BPHY_RS04915	BPHY_RS04940
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	BPHY_RS20500	BPHY_RS13270
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	BPHY_RS13655	BPHY_RS03820
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	BPHY_RS13655	BPHY_RS24290
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	BPHY_RS29790	BPHY_RS16730
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	BPHY_RS03670	BPHY_RS10220
bamI	class II benzoyl-CoA reductase, BamI subunit	BPHY_RS03665
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	BPHY_RS07840
boxB	benzoyl-CoA epoxidase, subunit B	BPHY_RS07845
boxC	2,3-epoxybenzoyl-CoA dihydrolase	BPHY_RS07850
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	BPHY_RS25695	BPHY_RS00875
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	BPHY_RS24290	BPHY_RS33205
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BPHY_RS13655	BPHY_RS24290
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	BPHY_RS01920	BPHY_RS35840
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
gcdH	glutaryl-CoA dehydrogenase	BPHY_RS12365	BPHY_RS18015
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hcl	4-hydroxybenzoyl-CoA ligase	BPHY_RS07865	BPHY_RS20530
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	BPHY_RS00465	BPHY_RS22865
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit	BPHY_RS23745	BPHY_RS25730
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	BPHY_RS00470	BPHY_RS23750
mhpD	2-hydroxypentadienoate hydratase	BPHY_RS22815	BPHY_RS17790
mhpE	4-hydroxy-2-oxovalerate aldolase	BPHY_RS22825	BPHY_RS17780
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
paaF	2,3-dehydroadipyl-CoA hydratase	BPHY_RS13655	BPHY_RS10120
paaH	3-hydroxyadipyl-CoA dehydrogenase	BPHY_RS01920	BPHY_RS35840
paaJ2	3-oxoadipyl-CoA thiolase	BPHY_RS19030	BPHY_RS13665
pcaB	3-carboxymuconate cycloisomerase	BPHY_RS22430
pcaC	4-carboxymuconolactone decarboxylase	BPHY_RS22440	BPHY_RS22435
pcaD	3-oxoadipate enol-lactone hydrolase	BPHY_RS22435	BPHY_RS00965
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	BPHY_RS19030	BPHY_RS13665
pcaG	protocatechuate 3,4-dioxygenase, beta subunit	BPHY_RS19625
pcaH	protocatechuate 3,4-dioxygenase, alpha subunit	BPHY_RS19630	BPHY_RS19625
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)	BPHY_RS22420	BPHY_RS07975
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)	BPHY_RS22425	BPHY_RS07970
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	BPHY_RS05230	BPHY_RS01925
pimC	pimeloyl-CoA dehydrogenase, small subunit	BPHY_RS10155
pimD	pimeloyl-CoA dehydrogenase, large subunit	BPHY_RS10160	BPHY_RS18015
pimF	6-carboxyhex-2-enoyl-CoA hydratase	BPHY_RS05220	BPHY_RS35840
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	BPHY_RS28155	BPHY_RS23615
praC	2-hydroxymuconate tautomerase	BPHY_RS33820	BPHY_RS17075
praD	2-oxohex-3-enedioate decarboxylase	BPHY_RS17790	BPHY_RS22815
pta	phosphate acetyltransferase	BPHY_RS30920	BPHY_RS18620
xylF	2-hydroxymuconate semialdehyde hydrolase	BPHY_RS17805	BPHY_RS22835

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.