phenylacetate catabolism in Thauera aminoaromatica S2

GapMind for catabolism of small carbon sources

phenylacetate catabolism in Thauera aminoaromatica S2

Best path

ppa, paaK, padB, padC, padD, padG, padI, padE, padF, padH, bcrA, bcrB, bcrC, bcrD, dch, had, oah, pimB, gcdH, ech, fadB, atoB

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 (41 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
ppa	phenylacetate permease ppa	C665_RS12865	C665_RS13515
paaK	phenylacetate-CoA ligase	C665_RS03175	C665_RS06105
padB	phenylacetyl-CoA dehydrogenase, PadB subunit	C665_RS06145	C665_RS04875
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	C665_RS06140	C665_RS04870
padD	phenylacetyl-CoA dehydrogenase, PadD subunit	C665_RS06135
padG	phenylglyoxylate dehydrogenase, alpha subunit	C665_RS06120
padI	phenylglyoxylate dehydrogenase, beta subunit	C665_RS06110
padE	phenylglyoxylate dehydrogenase, gamma subunit	C665_RS06130
padF	phenylglyoxylate dehydrogenase, delta subunit	C665_RS06125
padH	phenylglyoxylate dehydrogenase, epsilon subunit	C665_RS06115	C665_RS03645
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	C665_RS06195
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit	C665_RS06190
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit	C665_RS06185
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	C665_RS06200	C665_RS06195
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	C665_RS06180	C665_RS11710
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	C665_RS06170	C665_RS04310
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	C665_RS06175
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	C665_RS04230	C665_RS03170
gcdH	glutaryl-CoA dehydrogenase	C665_RS15135	C665_RS12450
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	C665_RS16150	C665_RS16085
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	C665_RS04225	C665_RS00910
atoB	acetyl-CoA C-acetyltransferase	C665_RS12455	C665_RS01835
Alternative steps:
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	C665_RS01145	C665_RS01140
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	C665_RS11710	C665_RS10355
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	C665_RS16150	C665_RS16085
bamB	class II benzoyl-CoA reductase, BamB subunit	C665_RS03640
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	C665_RS07555	C665_RS05430
bamI	class II benzoyl-CoA reductase, BamI subunit	C665_RS07550	C665_RS17595
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
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	C665_RS12450	C665_RS13930
H281DRAFT_04042	phenylacetate:H+ symporter
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	C665_RS03160
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	C665_RS03155
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	C665_RS03150
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	C665_RS03140
paaF	2,3-dehydroadipyl-CoA hydratase	C665_RS16150	C665_RS16085
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	C665_RS03190	C665_RS11710
paaH	3-hydroxyadipyl-CoA dehydrogenase	C665_RS04225	C665_RS03185
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	C665_RS03170	C665_RS04230
paaJ2	3-oxoadipyl-CoA thiolase	C665_RS03170	C665_RS04230
paaT	phenylacetate transporter Paa
paaZ1	oxepin-CoA hydrolase	C665_RS03190	C665_RS16150
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	C665_RS03195
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit
pimF	6-carboxyhex-2-enoyl-CoA hydratase	C665_RS04215

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

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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