phenylacetate catabolism in Sedimenticola selenatireducens DSM 17993

GapMind for catabolism of small carbon sources

phenylacetate catabolism in Sedimenticola selenatireducens DSM 17993

Best path

paaT, paaK, padB, padC, padD, padG, padI, padE, padF, padH, boxA, boxB, boxC, boxD, 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 (38 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
paaT	phenylacetate transporter Paa
paaK	phenylacetate-CoA ligase	A3GO_RS0115380	A3GO_RS0115695
padB	phenylacetyl-CoA dehydrogenase, PadB subunit	A3GO_RS0115735	A3GO_RS0111485
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	A3GO_RS0115730	A3GO_RS0111480
padD	phenylacetyl-CoA dehydrogenase, PadD subunit	A3GO_RS0111475	A3GO_RS24140
padG	phenylglyoxylate dehydrogenase, alpha subunit	A3GO_RS0115710
padI	phenylglyoxylate dehydrogenase, beta subunit	A3GO_RS0115700
padE	phenylglyoxylate dehydrogenase, gamma subunit	A3GO_RS0115720
padF	phenylglyoxylate dehydrogenase, delta subunit	A3GO_RS0115715
padH	phenylglyoxylate dehydrogenase, epsilon subunit	A3GO_RS0115705	A3GO_RS0107860
boxA	benzoyl-CoA epoxidase, subunit A	A3GO_RS0113935
boxB	benzoyl-CoA epoxidase, subunit B	A3GO_RS0118600
boxC	2,3-epoxybenzoyl-CoA dihydrolase	A3GO_RS0118595
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	A3GO_RS0115405
paaF	2,3-dehydroadipyl-CoA hydratase	A3GO_RS0115400	A3GO_RS0104130
paaH	3-hydroxyadipyl-CoA dehydrogenase	A3GO_RS0115390	A3GO_RS0108695
paaJ2	3-oxoadipyl-CoA thiolase	A3GO_RS0115675	A3GO_RS0115385
Alternative steps:
atoB	acetyl-CoA C-acetyltransferase	A3GO_RS0108835	A3GO_RS0107785
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	A3GO_RS0104110	A3GO_RS0109385
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	A3GO_RS0109460	A3GO_RS0105700
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	A3GO_RS0104130	A3GO_RS0115400
bamB	class II benzoyl-CoA reductase, BamB subunit	A3GO_RS0107855
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	A3GO_RS0120600	A3GO_RS0108155
bamI	class II benzoyl-CoA reductase, BamI subunit
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	A3GO_RS0115785
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit	A3GO_RS0115780
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit	A3GO_RS0115775
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	A3GO_RS0115790	A3GO_RS0115785
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	A3GO_RS0114370	A3GO_RS0114380
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	A3GO_RS0115770	A3GO_RS0114405
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	A3GO_RS0114405	A3GO_RS0115400
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	A3GO_RS0108695	A3GO_RS0114400
gcdH	glutaryl-CoA dehydrogenase	A3GO_RS0115815	A3GO_RS0114380
H281DRAFT_04042	phenylacetate:H+ symporter
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	A3GO_RS0115760
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	A3GO_RS0115765
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	A3GO_RS0115395	A3GO_RS0108710
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	A3GO_RS0115385	A3GO_RS0115675
paaZ1	oxepin-CoA hydrolase	A3GO_RS0115405	A3GO_RS0115395
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	A3GO_RS0115405
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	A3GO_RS0108690	A3GO_RS0107785
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit
pimF	6-carboxyhex-2-enoyl-CoA hydratase
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