phenylacetate catabolism in Magnetospirillum magneticum AMB-1

GapMind for catabolism of small carbon sources

phenylacetate catabolism in Magnetospirillum magneticum AMB-1

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 (42 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
ppa	phenylacetate permease ppa	AMB_RS21920	AMB_RS13720
paaK	phenylacetate-CoA ligase	AMB_RS13855	AMB_RS06320
padB	phenylacetyl-CoA dehydrogenase, PadB subunit	AMB_RS06300	AMB_RS10170
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	AMB_RS10175	AMB_RS06305
padD	phenylacetyl-CoA dehydrogenase, PadD subunit	AMB_RS06310	AMB_RS10180
padG	phenylglyoxylate dehydrogenase, alpha subunit	AMB_RS08485
padI	phenylglyoxylate dehydrogenase, beta subunit	AMB_RS08495
padE	phenylglyoxylate dehydrogenase, gamma subunit	AMB_RS08475
padF	phenylglyoxylate dehydrogenase, delta subunit	AMB_RS08480
padH	phenylglyoxylate dehydrogenase, epsilon subunit	AMB_RS08490	AMB_RS14720
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	AMB_RS10810
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit	AMB_RS10815
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit	AMB_RS10820
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	AMB_RS10805	AMB_RS10810
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	AMB_RS10825	AMB_RS03265
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	AMB_RS10835
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	AMB_RS10830
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	AMB_RS13850	AMB_RS04295
gcdH	glutaryl-CoA dehydrogenase	AMB_RS16315	AMB_RS03480
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	AMB_RS03265	AMB_RS13070
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	AMB_RS15050	AMB_RS19750
atoB	acetyl-CoA C-acetyltransferase	AMB_RS18210	AMB_RS04295
Alternative steps:
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	AMB_RS13035	AMB_RS13020
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	AMB_RS03265	AMB_RS13070
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	AMB_RS03265	AMB_RS13070
bamB	class II benzoyl-CoA reductase, BamB subunit	AMB_RS14710
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	AMB_RS13985	AMB_RS17165
bamI	class II benzoyl-CoA reductase, BamI subunit	AMB_RS00865	AMB_RS13980
boxA	benzoyl-CoA epoxidase, subunit A	AMB_RS00895
boxB	benzoyl-CoA epoxidase, subunit B	AMB_RS00890
boxC	2,3-epoxybenzoyl-CoA dihydrolase	AMB_RS00885
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	AMB_RS00880
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	AMB_RS18215	AMB_RS18150
H281DRAFT_04042	phenylacetate:H+ symporter
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
paaF	2,3-dehydroadipyl-CoA hydratase	AMB_RS03265	AMB_RS13070
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	AMB_RS00905	AMB_RS20905
paaH	3-hydroxyadipyl-CoA dehydrogenase	AMB_RS15050	AMB_RS19750
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	AMB_RS13850	AMB_RS13060
paaJ2	3-oxoadipyl-CoA thiolase	AMB_RS13850	AMB_RS13060
paaT	phenylacetate transporter Paa
paaZ1	oxepin-CoA hydrolase	AMB_RS00880	AMB_RS00905
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	AMB_RS00880
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit	AMB_RS03480
pimF	6-carboxyhex-2-enoyl-CoA hydratase	AMB_RS15050

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 17 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