L-phenylalanine catabolism in Rhodopseudomonas palustris CGA009

Best path

livF, livG, livH, livM, livJ, ARO8, ARO10, pad-dh, paaK, paaA, paaB, paaC, paaE, paaG, paaZ1, paaZ2, paaJ1, paaF, paaH, paaJ2

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 (55 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	TX73_RS19440	TX73_RS08940
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	TX73_RS19435	TX73_RS20510
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	TX73_RS19425	TX73_RS20500
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	TX73_RS19430	TX73_RS19000
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	TX73_RS19445
ARO8	L-phenylalanine transaminase	TX73_RS22075	TX73_RS21975
ARO10	phenylpyruvate decarboxylase	TX73_RS15890
pad-dh	phenylacetaldehyde dehydrogenase	TX73_RS06160	TX73_RS00575
paaK	phenylacetate-CoA ligase	TX73_RS08795	TX73_RS06275
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	TX73_RS19230
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	TX73_RS19225
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	TX73_RS19220
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	TX73_RS19210
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	TX73_RS08970	TX73_RS16860
paaZ1	oxepin-CoA hydrolase	TX73_RS08805	TX73_RS02510
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	TX73_RS08805
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	TX73_RS02660	TX73_RS02750
paaF	2,3-dehydroadipyl-CoA hydratase	TX73_RS03360	TX73_RS09240
paaH	3-hydroxyadipyl-CoA dehydrogenase	TX73_RS18975	TX73_RS04220
paaJ2	3-oxoadipyl-CoA thiolase	TX73_RS02660	TX73_RS02750
Alternative steps:
aacS	acetoacetyl-CoA synthetase	TX73_RS02400	TX73_RS16830
aroP	L-phenylalanine:H+ symporter AroP
atoA	acetoacetyl-CoA transferase, A subunit	TX73_RS21210
atoB	acetyl-CoA C-acetyltransferase	TX73_RS02750	TX73_RS11750
atoD	acetoacetyl-CoA transferase, B subunit	TX73_RS21205
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	TX73_RS03380	TX73_RS05675
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	TX73_RS03375	TX73_RS10930
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	TX73_RS03360	TX73_RS09240
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	TX73_RS03780	TX73_RS21725
bamI	class II benzoyl-CoA reductase, BamI subunit	TX73_RS03785
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	TX73_RS03405
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit	TX73_RS03400
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit	TX73_RS03395
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	TX73_RS03410	TX73_RS03405
boxA	benzoyl-CoA epoxidase, subunit A
boxB	benzoyl-CoA epoxidase, subunit B	TX73_RS03495
boxC	2,3-epoxybenzoyl-CoA dihydrolase	TX73_RS03490
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	TX73_RS08805
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	TX73_RS11755	TX73_RS08230
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	TX73_RS09240	TX73_RS22025
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	TX73_RS09240	TX73_RS22125
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	TX73_RS18975	TX73_RS04220
fahA	fumarylacetoacetate hydrolase	TX73_RS23885	TX73_RS20375
gcdH	glutaryl-CoA dehydrogenase	TX73_RS05595	TX73_RS08230
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase	TX73_RS23895
HPD	4-hydroxyphenylpyruvate dioxygenase	TX73_RS00025
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit	TX73_RS06250
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	TX73_RS16300
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit	TX73_RS06255
maiA	maleylacetoacetate isomerase	TX73_RS23890	TX73_RS22080
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
PAH	phenylalanine 4-monooxygenase
PCBD	pterin-4-alpha-carbinoalamine dehydratase	TX73_RS02095
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	TX73_RS18965	TX73_RS02750
pimC	pimeloyl-CoA dehydrogenase, small subunit	TX73_RS18955	TX73_RS06315
pimD	pimeloyl-CoA dehydrogenase, large subunit	TX73_RS18960	TX73_RS06310
pimF	6-carboxyhex-2-enoyl-CoA hydratase	TX73_RS18975	TX73_RS04220
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	TX73_RS14625	TX73_RS20025
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	TX73_RS14620	TX73_RS20020
QDPR	6,7-dihydropteridine reductase

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.