4-hydroxybenzoate catabolism in Rhizorhabdus wittichii RW1

Best path

pcaK, pobA, pcaH, pcaG, pcaB, pcaC, pcaD, pcaI, pcaJ, pcaF

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 (49 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
pcaK	4-hydroxybenzoate transporter pcaK	SWIT_RS21460
pobA	4-hydroxybenzoate 3-monooxygenase
pcaH	protocatechuate 3,4-dioxygenase, alpha subunit	SWIT_RS05460	SWIT_RS05465
pcaG	protocatechuate 3,4-dioxygenase, beta subunit	SWIT_RS05465	SWIT_RS05460
pcaB	3-carboxymuconate cycloisomerase	SWIT_RS05455	SWIT_RS22605
pcaC	4-carboxymuconolactone decarboxylase	SWIT_RS05450	SWIT_RS04985
pcaD	3-oxoadipate enol-lactone hydrolase	SWIT_RS04985	SWIT_RS05450
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)	SWIT_RS21935	SWIT_RS04890
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)	SWIT_RS21930	SWIT_RS26190
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	SWIT_RS26185	SWIT_RS21925
Alternative steps:
ackA	acetate kinase	SWIT_RS22145
acs	acetyl-CoA synthetase, AMP-forming	SWIT_RS17565	SWIT_RS03515
adh	acetaldehyde dehydrogenase (not acylating)	SWIT_RS03590	SWIT_RS08815
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	SWIT_RS26330	SWIT_RS10665
atoB	acetyl-CoA C-acetyltransferase	SWIT_RS03220	SWIT_RS10105
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	SWIT_RS10635	SWIT_RS16780
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	SWIT_RS09250	SWIT_RS05165
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	SWIT_RS03300	SWIT_RS09105
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	SWIT_RS07470
bamH	class II benzoyl-CoA reductase, BamH subunit	SWIT_RS07465	SWIT_RS15110
bamI	class II benzoyl-CoA reductase, BamI subunit	SWIT_RS07460
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
boxB	benzoyl-CoA epoxidase, subunit B
boxC	2,3-epoxybenzoyl-CoA dihydrolase
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	SWIT_RS03815
catI	3-oxoadipate CoA-transferase subunit A (CatI)
catJ	3-oxoadipate CoA-transferase subunit B (CatJ)	SWIT_RS16640
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	SWIT_RS03310	SWIT_RS08910
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	SWIT_RS27240	SWIT_RS09625
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	SWIT_RS09105	SWIT_RS03300
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	SWIT_RS14665	SWIT_RS10110
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	SWIT_RS04185	SWIT_RS21415
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hcl	4-hydroxybenzoyl-CoA ligase	SWIT_RS04220	SWIT_RS22100
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	SWIT_RS04250	SWIT_RS02535
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit	SWIT_RS25755
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	SWIT_RS25750	SWIT_RS02530
ligA	protocatechuate 4,5-dioxygenase, alpha subunit
ligB	protocatechuate 4,5-dioxygenase, beta subunit	SWIT_RS15485
ligC	2-hydroxy-4-carboxymuconate-6-semialdehyde dehydrogenase
ligI	2-pyrone-4,6-dicarboxylate hydrolase
ligJ	4-carboxy-2-hydroxymuconate hydratase	SWIT_RS15480
ligK	4-oxalocitramalate aldolase	SWIT_RS15515	SWIT_RS02415
ligU	4-oxalomesaconate tautomerase	SWIT_RS24190
mhpD	2-hydroxypentadienoate hydratase	SWIT_RS17805	SWIT_RS04640
mhpE	4-hydroxy-2-oxovalerate aldolase	SWIT_RS10670	SWIT_RS26325
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
paaF	2,3-dehydroadipyl-CoA hydratase	SWIT_RS03865	SWIT_RS03300
paaH	3-hydroxyadipyl-CoA dehydrogenase	SWIT_RS03825	SWIT_RS14665
paaJ2	3-oxoadipyl-CoA thiolase	SWIT_RS26185	SWIT_RS03835
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	SWIT_RS18385	SWIT_RS01725
pimC	pimeloyl-CoA dehydrogenase, small subunit	SWIT_RS01590	SWIT_RS01875
pimD	pimeloyl-CoA dehydrogenase, large subunit	SWIT_RS01585	SWIT_RS01880
pimF	6-carboxyhex-2-enoyl-CoA hydratase	SWIT_RS01610	SWIT_RS04215
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	SWIT_RS17800	SWIT_RS08815
praC	2-hydroxymuconate tautomerase	SWIT_RS19285
praD	2-oxohex-3-enedioate decarboxylase	SWIT_RS04645	SWIT_RS17810
pta	phosphate acetyltransferase	SWIT_RS13975
xylF	2-hydroxymuconate semialdehyde hydrolase	SWIT_RS08860	SWIT_RS26215

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.