4-hydroxybenzoate catabolism in Sinorhizobium medicae WSM419

GapMind for catabolism of small carbon sources

4-hydroxybenzoate catabolism in Sinorhizobium medicae WSM419

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 (37 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
pcaK	4-hydroxybenzoate transporter pcaK
pobA	4-hydroxybenzoate 3-monooxygenase	SMED_RS21040
pcaH	protocatechuate 3,4-dioxygenase, alpha subunit	SMED_RS21075
pcaG	protocatechuate 3,4-dioxygenase, beta subunit	SMED_RS21070	SMED_RS21075
pcaB	3-carboxymuconate cycloisomerase	SMED_RS21080	SMED_RS07490
pcaC	4-carboxymuconolactone decarboxylase	SMED_RS21065	SMED_RS08420
pcaD	3-oxoadipate enol-lactone hydrolase	SMED_RS21060	SMED_RS08420
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)	SMED_RS25350
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)	SMED_RS25355
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	SMED_RS25360	SMED_RS15645
Alternative steps:
ackA	acetate kinase	SMED_RS23375
acs	acetyl-CoA synthetase, AMP-forming	SMED_RS16020	SMED_RS16030
adh	acetaldehyde dehydrogenase (not acylating)	SMED_RS23160	SMED_RS24290
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
atoB	acetyl-CoA C-acetyltransferase	SMED_RS15645	SMED_RS25365
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	SMED_RS15640	SMED_RS03705
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	SMED_RS17950	SMED_RS20795
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	SMED_RS17950	SMED_RS11005
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	SMED_RS18170	SMED_RS14550
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
boxC	2,3-epoxybenzoyl-CoA dihydrolase
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	SMED_RS20785
catI	3-oxoadipate CoA-transferase subunit A (CatI)
catJ	3-oxoadipate CoA-transferase subunit B (CatJ)
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	SMED_RS22665	SMED_RS21235
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	SMED_RS17950	SMED_RS11005
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	SMED_RS17950	SMED_RS11005
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	SMED_RS00725	SMED_RS12690
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	SMED_RS25560	SMED_RS12385
gcdH	glutaryl-CoA dehydrogenase	SMED_RS23355	SMED_RS22665
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hcl	4-hydroxybenzoyl-CoA ligase	SMED_RS12625
hcrA	4-hydroxybenzoyl-CoA reductase, alpha subunit	SMED_RS20060	SMED_RS14470
hcrB	4-hydroxybenzoyl-CoA reductase, beta subunit	SMED_RS23660
hcrC	4-hydroxybenzoyl-CoA reductase, gamma subunit	SMED_RS20065	SMED_RS14475
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
ligJ	4-carboxy-2-hydroxymuconate hydratase
ligK	4-oxalocitramalate aldolase	SMED_RS29185
ligU	4-oxalomesaconate tautomerase
mhpD	2-hydroxypentadienoate hydratase
mhpE	4-hydroxy-2-oxovalerate aldolase	SMED_RS16165
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
paaF	2,3-dehydroadipyl-CoA hydratase	SMED_RS17950	SMED_RS11005
paaH	3-hydroxyadipyl-CoA dehydrogenase	SMED_RS00725	SMED_RS12690
paaJ2	3-oxoadipyl-CoA thiolase	SMED_RS25360	SMED_RS15645
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	SMED_RS15645	SMED_RS25360
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit
pimF	6-carboxyhex-2-enoyl-CoA hydratase	SMED_RS20800	SMED_RS00725
praA	protocatechuate 2,3-dioxygenase
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	SMED_RS11280	SMED_RS02820
praC	2-hydroxymuconate tautomerase
praD	2-oxohex-3-enedioate decarboxylase
pta	phosphate acetyltransferase	SMED_RS24255	SMED_RS23370
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 Apr 09 2024. 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 2024 update 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