4-hydroxybenzoate catabolism in Sphingomonas histidinilytica UM2

Best path

pcaK, pobA, praA, praB, praC, praD, mhpD, mhpE, ald-dh-CoA

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 (46 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
pcaK	4-hydroxybenzoate transporter pcaK	B5X82_RS00855	B5X82_RS19690
pobA	4-hydroxybenzoate 3-monooxygenase
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	B5X82_RS03860	B5X82_RS21475
praC	2-hydroxymuconate tautomerase	B5X82_RS21435	B5X82_RS05105
praD	2-oxohex-3-enedioate decarboxylase	B5X82_RS06655	B5X82_RS21450
mhpD	2-hydroxypentadienoate hydratase	B5X82_RS03865	B5X82_RS21455
mhpE	4-hydroxy-2-oxovalerate aldolase	B5X82_RS20940	B5X82_RS11335
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	B5X82_RS20945
Alternative steps:
ackA	acetate kinase	B5X82_RS10990
acs	acetyl-CoA synthetase, AMP-forming	B5X82_RS24705	B5X82_RS19755
adh	acetaldehyde dehydrogenase (not acylating)	B5X82_RS24620	B5X82_RS22235
atoB	acetyl-CoA C-acetyltransferase	B5X82_RS18105	B5X82_RS24295
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	B5X82_RS20980	B5X82_RS14100
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	B5X82_RS19870	B5X82_RS19780
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	B5X82_RS23095	B5X82_RS23050
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	B5X82_RS21655
bamH	class II benzoyl-CoA reductase, BamH subunit	B5X82_RS21650	B5X82_RS15110
bamI	class II benzoyl-CoA reductase, BamI subunit	B5X82_RS21645
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	B5X82_RS23045
catI	3-oxoadipate CoA-transferase subunit A (CatI)
catJ	3-oxoadipate CoA-transferase subunit B (CatJ)	B5X82_RS14260
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	B5X82_RS24130	B5X82_RS22330
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	B5X82_RS16885	B5X82_RS16345
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	B5X82_RS19780	B5X82_RS16280
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	B5X82_RS15560	B5X82_RS24290
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	B5X82_RS04280	B5X82_RS20685
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hcl	4-hydroxybenzoyl-CoA ligase	B5X82_RS20350	B5X82_RS11035
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	B5X82_RS11490	B5X82_RS11780
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	B5X82_RS11775	B5X82_RS16150
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	B5X82_RS20160	B5X82_RS20175
ligJ	4-carboxy-2-hydroxymuconate hydratase	B5X82_RS20070
ligK	4-oxalocitramalate aldolase	B5X82_RS20210	B5X82_RS03570
ligU	4-oxalomesaconate tautomerase
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	B5X82_RS25360
paaF	2,3-dehydroadipyl-CoA hydratase	B5X82_RS23095	B5X82_RS19780
paaH	3-hydroxyadipyl-CoA dehydrogenase	B5X82_RS23055	B5X82_RS15560
paaJ2	3-oxoadipyl-CoA thiolase	B5X82_RS23065	B5X82_RS11200
pcaB	3-carboxymuconate cycloisomerase	B5X82_RS10685
pcaC	4-carboxymuconolactone decarboxylase	B5X82_RS04455	B5X82_RS21260
pcaD	3-oxoadipate enol-lactone hydrolase	B5X82_RS06950	B5X82_RS15680
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	B5X82_RS11200	B5X82_RS23065
pcaG	protocatechuate 3,4-dioxygenase, beta subunit
pcaH	protocatechuate 3,4-dioxygenase, alpha subunit
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)	B5X82_RS11190	B5X82_RS06855
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)	B5X82_RS11195	B5X82_RS24530
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	B5X82_RS04605	B5X82_RS03015
pimC	pimeloyl-CoA dehydrogenase, small subunit	B5X82_RS02875	B5X82_RS04520
pimD	pimeloyl-CoA dehydrogenase, large subunit	B5X82_RS02870	B5X82_RS04515
pimF	6-carboxyhex-2-enoyl-CoA hydratase	B5X82_RS02895	B5X82_RS20355
pta	phosphate acetyltransferase	B5X82_RS16895
xylF	2-hydroxymuconate semialdehyde hydrolase	B5X82_RS22280	B5X82_RS11830

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.