phenylacetate catabolism in Roseateles aquatilis CCUG 48205

GapMind for catabolism of small carbon sources

phenylacetate catabolism in Roseateles aquatilis CCUG 48205

Best path

paaT, paaK, paaA, paaB, paaC, paaE, paaG, paaZ1, paaZ2, paaJ1, paaF, paaH, paaJ2

Rules

Overview: Phenylacetate utilization in GapMind is based on MetaCyc pathway phenylacetate degradation I (aerobic via phenylacetyl-CoA dehydrogenase, link) and pathway II (anaerobic via benzoyl-CoA, link).

all: phenylacetate-transport and phenylacetate-degradation
phenylacetate-degradation: paaK and phenylacetyl-CoA-degradation

Comment: Phenylacetate is activated to phenylacetyl-CoA by paaK

phenylacetyl-CoA-degradation:

paaA, paaB, paaC, paaE, paaG, paaZ1, paaZ2, paaJ1, paaF, paaH and paaJ2
or phenylacetyl-CoA-dehydrogenase, phenylglyoxylate-dehydrogenase and benzoyl-CoA-degradation
Comment: In the aerobic pathway, oxygen-dependent 1,2-epoxidase (PaaABCE) converts phenylacetyl-CoA to 1,2-epoxyphenylacetyl-CoA, which spontaenously rearranges to 2-(oxepinyl)acetyl-CoA; isomerase PaaG forms 2-oxepin-2(3H)-ylideneacetyl-CoA ("oxepin-CoA"); a ring-opening hydrolase forms 3-oxo-5,6-didehydrosuberyl-CoA semialdehyde; a dehydrogenase forms 3-oxo-5,6-didehydrosuberyl-CoA; thiolase PaaJ forms cis-3,4-didehydroadipyl-CoA (and acetyl-CoA); isomerase PaaG forms trans-2,3-didehydroadipyl-CoA; hydratase PaaF forms (3S)-hydroxyadipyl-CoA; dehydrogenase PaaH forms 3-oxoadipyl-CoA, and thiolase PaaJ forms succinyl-CoA and acetyl-CoA. (The role of PaaG is described in PMID:31689071 and differs slightly from MetaCyc.) In the anaerobic pathway, a dehydrogenase forms phenylglyoxyl-CoA, a hydrolase forms phenylglyoxylate (this step is not linked to sequence but is likely provided by the phenylglyoxylyl-CoA dehydrogenase, see PMID:10336636), and another dehydrogenase forms benzoyl-CoA and CO2. In principle, this pathway could occur aerobically, so GapMind includes aerobic pathways for degrading the benzoyl-CoA.

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.

phenylacetyl-CoA-dehydrogenase: padB, padC and padD
phenylglyoxylate-dehydrogenase: padG, padI, padE, padF and padH
phenylacetate-transport:

paaT
or ppa
or H281DRAFT_04042
Comment: Transporters were identified using query: transporter:phenylacetate

54 steps (27 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
paaT	phenylacetate transporter Paa
paaK	phenylacetate-CoA ligase	CDN99_RS09995	CDN99_RS04330
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	CDN99_RS10000
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	CDN99_RS10005
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	CDN99_RS10010
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	CDN99_RS10020
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	CDN99_RS09985	CDN99_RS14525
paaZ1	oxepin-CoA hydrolase	CDN99_RS10035	CDN99_RS09985
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	CDN99_RS10035
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	CDN99_RS25360	CDN99_RS22545
paaF	2,3-dehydroadipyl-CoA hydratase	CDN99_RS17935	CDN99_RS09985
paaH	3-hydroxyadipyl-CoA dehydrogenase	CDN99_RS04890	CDN99_RS22535
paaJ2	3-oxoadipyl-CoA thiolase	CDN99_RS25360	CDN99_RS22545
Alternative steps:
atoB	acetyl-CoA C-acetyltransferase	CDN99_RS02845	CDN99_RS12975
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	CDN99_RS14510	CDN99_RS02840
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	CDN99_RS17935
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	CDN99_RS17935	CDN99_RS02600
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	CDN99_RS06030
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	CDN99_RS10035
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	CDN99_RS12965	CDN99_RS12990
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	CDN99_RS17935	CDN99_RS22530
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	CDN99_RS17935	CDN99_RS02600
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	CDN99_RS04890	CDN99_RS02600
gcdH	glutaryl-CoA dehydrogenase	CDN99_RS14575	CDN99_RS12990
H281DRAFT_04042	phenylacetate:H+ symporter
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit
padD	phenylacetyl-CoA dehydrogenase, PadD subunit
padE	phenylglyoxylate dehydrogenase, gamma subunit
padF	phenylglyoxylate dehydrogenase, delta subunit
padG	phenylglyoxylate dehydrogenase, alpha subunit
padH	phenylglyoxylate dehydrogenase, epsilon subunit
padI	phenylglyoxylate dehydrogenase, beta subunit
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	CDN99_RS02595	CDN99_RS04885
pimC	pimeloyl-CoA dehydrogenase, small subunit	CDN99_RS15095
pimD	pimeloyl-CoA dehydrogenase, large subunit	CDN99_RS15100
pimF	6-carboxyhex-2-enoyl-CoA hydratase	CDN99_RS02600	CDN99_RS12460
ppa	phenylacetate permease ppa

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.

Downloads

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