4-hydroxybenzoate catabolism in Bradyrhizobium diazoefficiens USDA110

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 (48 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
pcaK	4-hydroxybenzoate transporter pcaK
pobA	4-hydroxybenzoate 3-monooxygenase	BJA_RS20995	BJA_RS11440
pcaH	protocatechuate 3,4-dioxygenase, alpha subunit	BJA_RS11425	BJA_RS04695
pcaG	protocatechuate 3,4-dioxygenase, beta subunit	BJA_RS11420	BJA_RS04690
pcaB	3-carboxymuconate cycloisomerase	BJA_RS28680	BJA_RS40325
pcaC	4-carboxymuconolactone decarboxylase	BJA_RS28690	BJA_RS07055
pcaD	3-oxoadipate enol-lactone hydrolase	BJA_RS28685
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)	BJA_RS35965	BJA_RS17175
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)	BJA_RS35960	BJA_RS17170
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	BJA_RS04680	BJA_RS18410
Alternative steps:
ackA	acetate kinase	BJA_RS12375	BJA_RS17155
acs	acetyl-CoA synthetase, AMP-forming	BJA_RS02905	BJA_RS19625
adh	acetaldehyde dehydrogenase (not acylating)	BJA_RS24030	BJA_RS38580
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
atoB	acetyl-CoA C-acetyltransferase	BJA_RS18410	BJA_RS39620
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	BJA_RS19400	BJA_RS10570
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	BJA_RS30585	BJA_RS00720
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	BJA_RS15040	BJA_RS32235
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	BJA_RS15560	BJA_RS24700
bamI	class II benzoyl-CoA reductase, BamI subunit
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	BJA_RS05470
boxC	2,3-epoxybenzoyl-CoA dihydrolase	BJA_RS05465
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	BJA_RS22060	BJA_RS19610
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	BJA_RS13075	BJA_RS15040
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BJA_RS15040	BJA_RS32235
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	BJA_RS31520	BJA_RS39695
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	BJA_RS36380	BJA_RS34425
gcdH	glutaryl-CoA dehydrogenase	BJA_RS12935	BJA_RS22060
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	BJA_RS30720
hcl	4-hydroxybenzoyl-CoA ligase	BJA_RS05450	BJA_RS00530
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	BJA_RS31190	BJA_RS01685
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit	BJA_RS10820	BJA_RS26265
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	BJA_RS16745	BJA_RS31595
ligA	protocatechuate 4,5-dioxygenase, alpha subunit
ligB	protocatechuate 4,5-dioxygenase, beta subunit
ligC	2-hydroxy-4-carboxymuconate-6-semialdehyde dehydrogenase	BJA_RS18145
ligI	2-pyrone-4,6-dicarboxylate hydrolase	BJA_RS19020	BJA_RS11145
ligJ	4-carboxy-2-hydroxymuconate hydratase	BJA_RS19030
ligK	4-oxalocitramalate aldolase	BJA_RS19035	BJA_RS18040
ligU	4-oxalomesaconate tautomerase
mhpD	2-hydroxypentadienoate hydratase	BJA_RS14730	BJA_RS06285
mhpE	4-hydroxy-2-oxovalerate aldolase	BJA_RS14745	BJA_RS28875
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	BJA_RS28345
paaF	2,3-dehydroadipyl-CoA hydratase	BJA_RS15040	BJA_RS32235
paaH	3-hydroxyadipyl-CoA dehydrogenase	BJA_RS31520	BJA_RS39695
paaJ2	3-oxoadipyl-CoA thiolase	BJA_RS04680	BJA_RS18410
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	BJA_RS39685	BJA_RS37530
pimC	pimeloyl-CoA dehydrogenase, small subunit	BJA_RS39675	BJA_RS36860
pimD	pimeloyl-CoA dehydrogenase, large subunit	BJA_RS39680	BJA_RS36865
pimF	6-carboxyhex-2-enoyl-CoA hydratase	BJA_RS39695	BJA_RS05890
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	BJA_RS14720	BJA_RS18690
praC	2-hydroxymuconate tautomerase	BJA_RS37825	BJA_RS37010
praD	2-oxohex-3-enedioate decarboxylase	BJA_RS06285	BJA_RS14730
pta	phosphate acetyltransferase	BJA_RS17150	BJA_RS18420
xylF	2-hydroxymuconate semialdehyde hydrolase

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.