4-hydroxybenzoate catabolism in Magnetospirillum magneticum AMB-1

Best path

pcaK, hcl, hcrA, hcrB, hcrC, bcrA, bcrB, bcrC, bcrD, dch, had, oah, pimB, gcdH, ech, fadB, atoB

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 (52 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
pcaK	4-hydroxybenzoate transporter pcaK	AMB_RS01320	AMB_RS22655
hcl	4-hydroxybenzoyl-CoA ligase	AMB_RS14445	AMB_RS07835
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	AMB_RS10200	AMB_RS07490
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit	AMB_RS10205
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	AMB_RS10195	AMB_RS14510
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	AMB_RS10810
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit	AMB_RS10815
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit	AMB_RS10820
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	AMB_RS10805	AMB_RS10810
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	AMB_RS10825	AMB_RS03265
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	AMB_RS10835
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	AMB_RS10830
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	AMB_RS13850	AMB_RS04295
gcdH	glutaryl-CoA dehydrogenase	AMB_RS16315	AMB_RS03480
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	AMB_RS03265	AMB_RS13070
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	AMB_RS15050	AMB_RS19750
atoB	acetyl-CoA C-acetyltransferase	AMB_RS18210	AMB_RS04295
Alternative steps:
ackA	acetate kinase	AMB_RS12860
acs	acetyl-CoA synthetase, AMP-forming	AMB_RS21140	AMB_RS11645
adh	acetaldehyde dehydrogenase (not acylating)	AMB_RS18195	AMB_RS06710
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	AMB_RS13035	AMB_RS13020
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	AMB_RS03265	AMB_RS13070
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	AMB_RS03265	AMB_RS13070
bamB	class II benzoyl-CoA reductase, BamB subunit	AMB_RS14710
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	AMB_RS13985	AMB_RS17165
bamI	class II benzoyl-CoA reductase, BamI subunit	AMB_RS00865	AMB_RS13980
boxA	benzoyl-CoA epoxidase, subunit A	AMB_RS00895
boxB	benzoyl-CoA epoxidase, subunit B	AMB_RS00890
boxC	2,3-epoxybenzoyl-CoA dihydrolase	AMB_RS00885
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	AMB_RS00880
catI	3-oxoadipate CoA-transferase subunit A (CatI)
catJ	3-oxoadipate CoA-transferase subunit B (CatJ)
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	AMB_RS18215	AMB_RS18150
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	AMB_RS04130	AMB_RS02190
ligA	protocatechuate 4,5-dioxygenase, alpha subunit	AMB_RS01305
ligB	protocatechuate 4,5-dioxygenase, beta subunit	AMB_RS01310
ligC	2-hydroxy-4-carboxymuconate-6-semialdehyde dehydrogenase	AMB_RS01295
ligI	2-pyrone-4,6-dicarboxylate hydrolase	AMB_RS01290
ligJ	4-carboxy-2-hydroxymuconate hydratase	AMB_RS01275
ligK	4-oxalocitramalate aldolase	AMB_RS01280
ligU	4-oxalomesaconate tautomerase	AMB_RS01270
mhpD	2-hydroxypentadienoate hydratase	AMB_RS04100
mhpE	4-hydroxy-2-oxovalerate aldolase	AMB_RS04095
paaF	2,3-dehydroadipyl-CoA hydratase	AMB_RS03265	AMB_RS13070
paaH	3-hydroxyadipyl-CoA dehydrogenase	AMB_RS15050	AMB_RS19750
paaJ2	3-oxoadipyl-CoA thiolase	AMB_RS13850	AMB_RS13060
pcaB	3-carboxymuconate cycloisomerase
pcaC	4-carboxymuconolactone decarboxylase	AMB_RS20060
pcaD	3-oxoadipate enol-lactone hydrolase
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	AMB_RS13850	AMB_RS13060
pcaG	protocatechuate 3,4-dioxygenase, beta subunit
pcaH	protocatechuate 3,4-dioxygenase, alpha subunit
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit	AMB_RS03480
pimF	6-carboxyhex-2-enoyl-CoA hydratase	AMB_RS15050
pobA	4-hydroxybenzoate 3-monooxygenase	AMB_RS01315
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	AMB_RS04115	AMB_RS18195
praC	2-hydroxymuconate tautomerase
praD	2-oxohex-3-enedioate decarboxylase	AMB_RS04100
pta	phosphate acetyltransferase	AMB_RS12865	AMB_RS01465
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 17 2021. The underlying query database was built on Sep 17 2021.