L-phenylalanine catabolism in Rhodopseudomonas pseudopalustris DSM 123

Best path

livF, livG, livH, livM, livJ, ARO8, ARO10, pad-dh, paaK, padB, padC, padD, padG, padI, padE, padF, padH, bcrA, bcrB, bcrC, bcrD, Ch1CoA, badK, badH, badI, pimD, pimC, pimF, gcdH, ech, fadB, 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 (62 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	BMY71_RS09145	BMY71_RS02045
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	BMY71_RS09150	BMY71_RS14870
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	BMY71_RS09160	BMY71_RS17340
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	BMY71_RS09155	BMY71_RS17335
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	BMY71_RS09140
ARO8	L-phenylalanine transaminase	BMY71_RS21275	BMY71_RS21180
ARO10	phenylpyruvate decarboxylase	BMY71_RS19810
pad-dh	phenylacetaldehyde dehydrogenase	BMY71_RS01975	BMY71_RS08135
paaK	phenylacetate-CoA ligase	BMY71_RS09410	BMY71_RS14855
padB	phenylacetyl-CoA dehydrogenase, PadB subunit	BMY71_RS14815
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	BMY71_RS14820
padD	phenylacetyl-CoA dehydrogenase, PadD subunit	BMY71_RS14825
padG	phenylglyoxylate dehydrogenase, alpha subunit	BMY71_RS14840
padI	phenylglyoxylate dehydrogenase, beta subunit	BMY71_RS14850
padE	phenylglyoxylate dehydrogenase, gamma subunit	BMY71_RS14830
padF	phenylglyoxylate dehydrogenase, delta subunit	BMY71_RS14835
padH	phenylglyoxylate dehydrogenase, epsilon subunit	BMY71_RS14845
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	BMY71_RS14960
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit	BMY71_RS14965
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit	BMY71_RS14970
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	BMY71_RS14955
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	BMY71_RS08460	BMY71_RS16335
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	BMY71_RS15005	BMY71_RS09800
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	BMY71_RS14985	BMY71_RS00335
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	BMY71_RS14990	BMY71_RS10980
pimD	pimeloyl-CoA dehydrogenase, large subunit	BMY71_RS07930	BMY71_RS21555
pimC	pimeloyl-CoA dehydrogenase, small subunit	BMY71_RS07925	BMY71_RS21550
pimF	6-carboxyhex-2-enoyl-CoA hydratase	BMY71_RS07945
gcdH	glutaryl-CoA dehydrogenase	BMY71_RS04750	BMY71_RS08460
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BMY71_RS09800	BMY71_RS15005
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	BMY71_RS07945	BMY71_RS13930
atoB	acetyl-CoA C-acetyltransferase	BMY71_RS08240	BMY71_RS16330
Alternative steps:
aacS	acetoacetyl-CoA synthetase	BMY71_RS03035	BMY71_RS04345
aroP	L-phenylalanine:H+ symporter AroP
atoA	acetoacetyl-CoA transferase, A subunit	BMY71_RS05605
atoD	acetoacetyl-CoA transferase, B subunit	BMY71_RS05610
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	BMY71_RS19660	BMY71_RS05090
bamI	class II benzoyl-CoA reductase, BamI subunit	BMY71_RS19655
boxA	benzoyl-CoA epoxidase, subunit A
boxB	benzoyl-CoA epoxidase, subunit B	BMY71_RS13575
boxC	2,3-epoxybenzoyl-CoA dihydrolase	BMY71_RS13580
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	BMY71_RS09425
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	BMY71_RS09800	BMY71_RS21235
fahA	fumarylacetoacetate hydrolase	BMY71_RS03460
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase	BMY71_RS03450
HPD	4-hydroxyphenylpyruvate dioxygenase
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit	BMY71_RS21585
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	BMY71_RS16385
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit	BMY71_RS21580
maiA	maleylacetoacetate isomerase	BMY71_RS03455	BMY71_RS16145
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	BMY71_RS09420
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	BMY71_RS09385
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	BMY71_RS09390
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	BMY71_RS09395
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	BMY71_RS09405
paaF	2,3-dehydroadipyl-CoA hydratase	BMY71_RS15005	BMY71_RS09800
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	BMY71_RS09420	BMY71_RS09570
paaH	3-hydroxyadipyl-CoA dehydrogenase	BMY71_RS07945	BMY71_RS13930
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	BMY71_RS03380	BMY71_RS03310
paaJ2	3-oxoadipyl-CoA thiolase	BMY71_RS03380	BMY71_RS03310
paaZ1	oxepin-CoA hydrolase	BMY71_RS09425	BMY71_RS02035
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	BMY71_RS09425
PAH	phenylalanine 4-monooxygenase
PCBD	pterin-4-alpha-carbinoalamine dehydratase	BMY71_RS14385
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	BMY71_RS07935	BMY71_RS03310
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	BMY71_RS12375
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.