L-phenylalanine catabolism in Polaromonas naphthalenivorans CJ2

Best path

livF, livG, livH, livM, livJ, PAH, PCBD, QDPR, HPD, hmgA, maiA, fahA, atoA, atoD, atoB

Rules

Overview: Phenylalanine utilization in GapMind is based on MetaCyc pathway L-phenylalanine degradation I (aerobic, via tyrosine, link), pathway II (anaerobic, via phenylacetaldehyde dehydrogenase, link), degradation via phenylpyruvate:ferredoxin oxidoreductase (PMC3346364), or degradation via phenylacetaldehyde:ferredoxin oxidoreductase (PMID:24214948). (MetaCyc describes additional pathways, but they do not result in carbon incorporation or are not reported in prokaryotes, so they are not included in GapMind.)

• all:
  • phenylalanine-transport, ARO8, phenylpyruvate-fd-oxidoreductase and phenylacetyl-CoA-degradation
  • or phenylalanine-transport, ARO8, phenylpyruvate-decarboxylase, pad-dh and phenylacetate-degradation
  • or phenylalanine-transport, ARO8, phenylpyruvate-decarboxylase, pfor and phenylacetate-degradation
  • or phenylalanine-transport, PAH, PCBD, QDPR and tyrosine-degradation
  • Comment: Phenylalanine can be catabolized via transaminase ARO8, which forms phenylpyruvate (also known as 3-phenyl-2-oxo-propanoate), and phenylpyruvate:ferredoxin oxidoreductase, which forms phenylacetyl-CoA. In the anaerobic pathway, the transaminase ARO8 forms phenylpyruvate, a carboxy-lyase forms phenylacetaldehyde, and a dehydrogenase (pad-dh) forms phenylacetate Or, in a variation on the anaerobic pathway, the phenylacetaldehyde is oxidized to phenylacetate by phenylacetaldehyde:ferredoxin oxidoreductase (pfor). In the aerobic pathway, PAH forms tyrosine and hydroxylates its tetrahydropterin co-substrate; the tetrahydropterin is regenerated by dehydratase PCBD and reductase QDPR.
• phenylpyruvate-fd-oxidoreductase:
  • iorA and iorB
  • or iorAB
  • Comment: This enzyme is usually known as indolepyruvate:ferredoxin oxidoreductase, but it acts on phenylpyruvate as well, forming phenylacetyl-CoA (PMID:8206994). Phenylpyruvate:ferredoxin oxidoreductase has both heterodimeric (iorA/iorB) and fused (iorAB) forms.
• phenylpyruvate-decarboxylase:
  • ARO10
  • or PPDCalpha and PPDCbeta
  • Comment: Phenylpyruvate can be decarboxylated to phenylacetaldehyde by the typical homomeric enzyme, or by a heterodimer reported in Streptomyces virginiae (see PMID:28719183)
• 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.
• phenylacetate-degradation: paaK and phenylacetyl-CoA-degradation
  • Comment: Phenylacetate is activated to phenylacetyl-CoA by paaK
• 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).
• phenylglyoxylate-dehydrogenase: padG, padI, padE, padF and padH
• phenylacetyl-CoA-dehydrogenase: padB, padC and padD
• 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.
• tyrosine-degradation: HPD, hmgA, maiA, fahA and acetoacetate-degradation
  • Comment: In pathway I, an aminotransferase (not represented) forms 3-(4-hydroxyphenyl)pyruvate, dioxygenase HPD forms homogentisate, another oxygenase forms 4-maleyl-acetoacetate, an isomerase forms 4-fumaryl-acetoacetate, and a hydrolase yields acetoacetate and fumarate. (Fumarate is part of the TCA cycle so its catabolism is not described.)
• acetoacetate-degradation: acetoacetate-activation and atoB
  • Comment: The acetoacetate is activated to acetoacetyl-CoA, and cleaved by acetyl-CoA acetyltransferase, giving two acetyl-CoA.
• acetoacetate-activation:
  • atoA and atoD
  • or aacS
  • Comment: acetyl-CoA:acetoacetyl-CoA transferase (sometimes given EC 2.8.3.9 or EC 2.8.3.8) or succinyl-CoA:acetoacetyl-CoA transferase (EC 2.8.3.5, also known as 3-oxoacid CoA-transferase) can activate acetoacetate. These have an A and B subunit. Alternatively, an ATP-dependent ligase (aacS) can activate acetoacetate (EC 6.2.1.16).
• phenylalanine-transport:
  • livF, livG, livH, livM and livJ
  • or aroP
  • Comment: Transporters were identified using query: transporter:phenylalanine:L-phenylalanine:phe

76 steps (47 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	PNAP_RS15990	PNAP_RS17565
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	PNAP_RS15995	PNAP_RS17570
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	PNAP_RS16005	PNAP_RS17575
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	PNAP_RS16000	PNAP_RS17570
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	PNAP_RS10865	PNAP_RS19290
PAH	phenylalanine 4-monooxygenase	PNAP_RS05595
PCBD	pterin-4-alpha-carbinoalamine dehydratase	PNAP_RS07330
QDPR	6,7-dihydropteridine reductase	PNAP_RS06535
HPD	4-hydroxyphenylpyruvate dioxygenase	PNAP_RS05610	PNAP_RS08275
hmgA	homogentisate dioxygenase
maiA	maleylacetoacetate isomerase	PNAP_RS14020	PNAP_RS15735
fahA	fumarylacetoacetate hydrolase	PNAP_RS05600	PNAP_RS01495
atoA	acetoacetyl-CoA transferase, A subunit	PNAP_RS13280	PNAP_RS04300
atoD	acetoacetyl-CoA transferase, B subunit	PNAP_RS13275	PNAP_RS04305
atoB	acetyl-CoA C-acetyltransferase	PNAP_RS05805	PNAP_RS00315
Alternative steps:
aacS	acetoacetyl-CoA synthetase	PNAP_RS02330	PNAP_RS10700
ARO10	phenylpyruvate decarboxylase
ARO8	L-phenylalanine transaminase	PNAP_RS10420	PNAP_RS07800
aroP	L-phenylalanine:H+ symporter AroP
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	PNAP_RS10650	PNAP_RS11540
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	PNAP_RS10655	PNAP_RS16825
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	PNAP_RS10675	PNAP_RS16825
bamB	class II benzoyl-CoA reductase, BamB subunit	PNAP_RS00255
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	PNAP_RS07135	PNAP_RS04100
bamI	class II benzoyl-CoA reductase, BamI subunit	PNAP_RS07140
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	PNAP_RS14685
boxB	benzoyl-CoA epoxidase, subunit B	PNAP_RS14690
boxC	2,3-epoxybenzoyl-CoA dihydrolase	PNAP_RS14695
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	PNAP_RS14710
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	PNAP_RS02275	PNAP_RS02255
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	PNAP_RS16825	PNAP_RS10675
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	PNAP_RS16825	PNAP_RS10675
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	PNAP_RS17360	PNAP_RS10710
gcdH	glutaryl-CoA dehydrogenase	PNAP_RS10685	PNAP_RS05675
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	PNAP_RS19430
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
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	PNAP_RS16825	PNAP_RS10675
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	PNAP_RS09595	PNAP_RS18065
paaH	3-hydroxyadipyl-CoA dehydrogenase	PNAP_RS17360	PNAP_RS10710
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	PNAP_RS10715	PNAP_RS04310
paaJ2	3-oxoadipyl-CoA thiolase	PNAP_RS04310	PNAP_RS10715
paaK	phenylacetate-CoA ligase
paaZ1	oxepin-CoA hydrolase	PNAP_RS09595	PNAP_RS14710
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	PNAP_RS14710
pad-dh	phenylacetaldehyde dehydrogenase	PNAP_RS15070	PNAP_RS11115
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	PNAP_RS04150
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	PNAP_RS00260
padI	phenylglyoxylate dehydrogenase, beta subunit
pfor	phenylacetaldeyde:ferredoxin oxidoreductase	PNAP_RS00255
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	PNAP_RS09225	PNAP_RS17350
pimC	pimeloyl-CoA dehydrogenase, small subunit	PNAP_RS16090
pimD	pimeloyl-CoA dehydrogenase, large subunit	PNAP_RS16085	PNAP_RS10745
pimF	6-carboxyhex-2-enoyl-CoA hydratase	PNAP_RS09220	PNAP_RS10710
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit
PPDCbeta	phenylpyruvate decarboxylase, beta subunit

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.