4-hydroxybenzoate catabolism in Streptacidiphilus oryzae TH49

GapMind for catabolism of small carbon sources

4-hydroxybenzoate catabolism in Streptacidiphilus oryzae TH49

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 (50 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
pcaK	4-hydroxybenzoate transporter pcaK	BS73_RS06270
pobA	4-hydroxybenzoate 3-monooxygenase	BS73_RS09990	BS73_RS10270
pcaH	protocatechuate 3,4-dioxygenase, alpha subunit	BS73_RS10010	BS73_RS10015
pcaG	protocatechuate 3,4-dioxygenase, beta subunit	BS73_RS10015
pcaB	3-carboxymuconate cycloisomerase
pcaC	4-carboxymuconolactone decarboxylase	BS73_RS09995	BS73_RS15110
pcaD	3-oxoadipate enol-lactone hydrolase	BS73_RS09995	BS73_RS15110
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)	BS73_RS10025
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)	BS73_RS10020
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	BS73_RS12600	BS73_RS30630
Alternative steps:
ackA	acetate kinase	BS73_RS15005
acs	acetyl-CoA synthetase, AMP-forming	BS73_RS20690	BS73_RS01530
adh	acetaldehyde dehydrogenase (not acylating)	BS73_RS04090	BS73_RS01745
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
atoB	acetyl-CoA C-acetyltransferase	BS73_RS10365	BS73_RS08675
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	BS73_RS03225	BS73_RS09090
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	BS73_RS32220	BS73_RS07070
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	BS73_RS14910	BS73_RS05650
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	BS73_RS19015
bamE	class II benzoyl-CoA reductase, BamE subunit
bamF	class II benzoyl-CoA reductase, BamF subunit
bamG	class II benzoyl-CoA reductase, BamG subunit	BS73_RS32425
bamH	class II benzoyl-CoA reductase, BamH subunit	BS73_RS32420	BS73_RS21765
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	BS73_RS07420
boxC	2,3-epoxybenzoyl-CoA dihydrolase	BS73_RS07415
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase
catI	3-oxoadipate CoA-transferase subunit A (CatI)
catJ	3-oxoadipate CoA-transferase subunit B (CatJ)	BS73_RS10355
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	BS73_RS23895	BS73_RS08225
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	BS73_RS00915	BS73_RS14910
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BS73_RS14910	BS73_RS05650
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	BS73_RS08975	BS73_RS07230
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	BS73_RS32915	BS73_RS25270
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hcl	4-hydroxybenzoyl-CoA ligase	BS73_RS00385	BS73_RS27680
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	BS73_RS29680	BS73_RS33760
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit	BS73_RS05105	BS73_RS06285
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	BS73_RS24330	BS73_RS08345
ligA	protocatechuate 4,5-dioxygenase, alpha subunit
ligB	protocatechuate 4,5-dioxygenase, beta subunit
ligC	2-hydroxy-4-carboxymuconate-6-semialdehyde dehydrogenase	BS73_RS09795	BS73_RS01145
ligI	2-pyrone-4,6-dicarboxylate hydrolase	BS73_RS27585
ligJ	4-carboxy-2-hydroxymuconate hydratase	BS73_RS27580	BS73_RS32535
ligK	4-oxalocitramalate aldolase	BS73_RS32540	BS73_RS31825
ligU	4-oxalomesaconate tautomerase	BS73_RS31830	BS73_RS10825
mhpD	2-hydroxypentadienoate hydratase	BS73_RS04080	BS73_RS37045
mhpE	4-hydroxy-2-oxovalerate aldolase	BS73_RS11375
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	BS73_RS32220
paaF	2,3-dehydroadipyl-CoA hydratase	BS73_RS14910	BS73_RS20300
paaH	3-hydroxyadipyl-CoA dehydrogenase	BS73_RS08975	BS73_RS07230
paaJ2	3-oxoadipyl-CoA thiolase	BS73_RS30630	BS73_RS12600
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	BS73_RS15085	BS73_RS30630
pimC	pimeloyl-CoA dehydrogenase, small subunit	BS73_RS07080	BS73_RS00880
pimD	pimeloyl-CoA dehydrogenase, large subunit	BS73_RS07085	BS73_RS33675
pimF	6-carboxyhex-2-enoyl-CoA hydratase	BS73_RS06375	BS73_RS32280
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	BS73_RS01225	BS73_RS23595
praC	2-hydroxymuconate tautomerase	BS73_RS17890	BS73_RS04070
praD	2-oxohex-3-enedioate decarboxylase	BS73_RS04080	BS73_RS37045
pta	phosphate acetyltransferase
xylF	2-hydroxymuconate semialdehyde hydrolase	BS73_RS00370

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.

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Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
SQLite3 databases

Related tools

About GapMind

Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.

A candidate for a step is "high confidence" if either:

ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.

where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").

Otherwise, a candidate is "medium confidence" if either:

ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
HMMer finds a hit (regardless of coverage or other bits).

Other blast hits with at least 50% coverage are "low confidence."

Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:

our ignorance of proteins' functions,
omissions in the gene models,
frame-shift errors in the genome sequence, or
the organism lacks the pathway.

GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).

For more information, see:

the paper from 2019 on GapMind for amino acid biosynthesis
the paper from 2022 on GapMind for carbon sources
the source code
instructions for running GapMind on your computer

If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know

by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory

GapMind for catabolism of small carbon sources