4-hydroxybenzoate catabolism in Cupriavidus basilensis 4G11

Best path

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

Also see fitness data for the top candidates

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 (56 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
pcaK	4-hydroxybenzoate transporter pcaK	RR42_RS21935	RR42_RS31660
pobA	4-hydroxybenzoate 3-monooxygenase	RR42_RS21940
pcaH	protocatechuate 3,4-dioxygenase, alpha subunit	RR42_RS32060	RR42_RS32065
pcaG	protocatechuate 3,4-dioxygenase, beta subunit	RR42_RS32065	RR42_RS32060
pcaB	3-carboxymuconate cycloisomerase	RR42_RS32055	RR42_RS25850
pcaC	4-carboxymuconolactone decarboxylase	RR42_RS32050	RR42_RS10690
pcaD	3-oxoadipate enol-lactone hydrolase	RR42_RS21850	RR42_RS32050
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)	RR42_RS35925	RR42_RS10005
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)	RR42_RS35920	RR42_RS10010
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	RR42_RS35915	RR42_RS26090
Alternative steps:
ackA	acetate kinase	RR42_RS03800	RR42_RS22745
acs	acetyl-CoA synthetase, AMP-forming	RR42_RS13880	RR42_RS10650
adh	acetaldehyde dehydrogenase (not acylating)	RR42_RS34255	RR42_RS25005
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	RR42_RS27895	RR42_RS32630
atoB	acetyl-CoA C-acetyltransferase	RR42_RS07610	RR42_RS25455
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	RR42_RS23690	RR42_RS25125
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	RR42_RS23695	RR42_RS18250
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	RR42_RS23710	RR42_RS18250
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	RR42_RS03755	RR42_RS05535
bamI	class II benzoyl-CoA reductase, BamI subunit	RR42_RS05540
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	RR42_RS35120	RR42_RS07500
boxB	benzoyl-CoA epoxidase, subunit B	RR42_RS35125	RR42_RS07505
boxC	2,3-epoxybenzoyl-CoA dihydrolase	RR42_RS07510	RR42_RS35130
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	RR42_RS35145
catI	3-oxoadipate CoA-transferase subunit A (CatI)
catJ	3-oxoadipate CoA-transferase subunit B (CatJ)	RR42_RS31950
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	RR42_RS00895	RR42_RS28565
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	RR42_RS28050	RR42_RS23710
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	RR42_RS18250	RR42_RS23710
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	RR42_RS02510	RR42_RS36415
fcbT1	tripartite 4-hydroxybenzoate transporter, substrate-binding component FcbT1	RR42_RS24120
fcbT2	tripartite 4-hydroxybenzoate transporter, small DctQ-like component FcbT2	RR42_RS24115
fcbT3	tripartite 4-hydroxybenzoate transporter, large permease subunit FcbT3	RR42_RS24110	RR42_RS09080
gcdH	glutaryl-CoA dehydrogenase	RR42_RS15400	RR42_RS28565
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	RR42_RS34260
hcl	4-hydroxybenzoyl-CoA ligase	RR42_RS07520	RR42_RS35150
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	RR42_RS13630	RR42_RS02365
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	RR42_RS13620	RR42_RS02370
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	RR42_RS10620	RR42_RS23430
ligJ	4-carboxy-2-hydroxymuconate hydratase	RR42_RS27205	RR42_RS28355
ligK	4-oxalocitramalate aldolase	RR42_RS27210	RR42_RS12215
ligU	4-oxalomesaconate tautomerase	RR42_RS23050	RR42_RS11275
mhpD	2-hydroxypentadienoate hydratase	RR42_RS27885	RR42_RS32645
mhpE	4-hydroxy-2-oxovalerate aldolase	RR42_RS27900	RR42_RS32625
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	RR42_RS11095
paaF	2,3-dehydroadipyl-CoA hydratase	RR42_RS18250	RR42_RS23710
paaH	3-hydroxyadipyl-CoA dehydrogenase	RR42_RS02510	RR42_RS36415
paaJ2	3-oxoadipyl-CoA thiolase	RR42_RS35915	RR42_RS26090
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	RR42_RS25210	RR42_RS10260
pimC	pimeloyl-CoA dehydrogenase, small subunit	RR42_RS36390	RR42_RS36650
pimD	pimeloyl-CoA dehydrogenase, large subunit	RR42_RS05595	RR42_RS36645
pimF	6-carboxyhex-2-enoyl-CoA hydratase	RR42_RS35270	RR42_RS11095
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	RR42_RS05110	RR42_RS32650
praC	2-hydroxymuconate tautomerase	RR42_RS32635	RR42_RS15120
praD	2-oxohex-3-enedioate decarboxylase	RR42_RS32640	RR42_RS32645
pta	phosphate acetyltransferase	RR42_RS33690	RR42_RS03805
xylF	2-hydroxymuconate semialdehyde hydrolase	RR42_RS27870	RR42_RS31825

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 17 2021. The underlying query database was built on Sep 17 2021.