L-phenylalanine catabolism in Desulfatiglans anilini DSM 4660

Best path

livF, livG, livH, livM, livJ, ARO8, iorA, iorB, 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 (47 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	H567_RS0109140	H567_RS0107395
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	H567_RS23835	H567_RS0105910
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	H567_RS0109125	H567_RS0107410
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	H567_RS0109130	H567_RS0108380
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	H567_RS0109120
ARO8	L-phenylalanine transaminase	H567_RS0110915	H567_RS0101850
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit	H567_RS0115245	H567_RS0117925
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit	H567_RS0115240	H567_RS0107490
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
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	H567_RS24220	H567_RS0115155
paaZ1	oxepin-CoA hydrolase	H567_RS0115155	H567_RS0115475
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	H567_RS0110065	H567_RS0110730
paaF	2,3-dehydroadipyl-CoA hydratase	H567_RS0110895	H567_RS0115475
paaH	3-hydroxyadipyl-CoA dehydrogenase	H567_RS0110735	H567_RS0107440
paaJ2	3-oxoadipyl-CoA thiolase	H567_RS0110065	H567_RS0115465
Alternative steps:
aacS	acetoacetyl-CoA synthetase	H567_RS0110465	H567_RS0117445
ARO10	phenylpyruvate decarboxylase
aroP	L-phenylalanine:H+ symporter AroP
atoA	acetoacetyl-CoA transferase, A subunit
atoB	acetyl-CoA C-acetyltransferase	H567_RS0110910	H567_RS0110905
atoD	acetoacetyl-CoA transferase, B subunit
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	H567_RS0117980	H567_RS0117055
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	H567_RS0114955	H567_RS0110895
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	H567_RS0110895	H567_RS0120240
bamB	class II benzoyl-CoA reductase, BamB subunit	H567_RS0102020	H567_RS0121100
bamC	class II benzoyl-CoA reductase, BamC subunit	H567_RS0102025	H567_RS23815
bamD	class II benzoyl-CoA reductase, BamD subunit	H567_RS0120870	H567_RS0108265
bamE	class II benzoyl-CoA reductase, BamE subunit	H567_RS0120855	H567_RS0108270
bamF	class II benzoyl-CoA reductase, BamF subunit	H567_RS0120850	H567_RS26650
bamG	class II benzoyl-CoA reductase, BamG subunit	H567_RS0103085	H567_RS0110430
bamH	class II benzoyl-CoA reductase, BamH subunit	H567_RS0102625	H567_RS0103080
bamI	class II benzoyl-CoA reductase, BamI subunit	H567_RS0120685	H567_RS26855
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	H567_RS0113105	H567_RS0112245
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit	H567_RS0113110
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	H567_RS0113105	H567_RS0112245
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	H567_RS0117635	H567_RS0110890
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	H567_RS0106025	H567_RS0110895
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	H567_RS0110895	H567_RS0118000
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	H567_RS0110735	H567_RS0107440
fahA	fumarylacetoacetate hydrolase	H567_RS24120
gcdH	glutaryl-CoA dehydrogenase	H567_RS0110890	H567_RS0117975
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	H567_RS0106015
hmgA	homogentisate dioxygenase
HPD	4-hydroxyphenylpyruvate dioxygenase
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB
maiA	maleylacetoacetate isomerase
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	H567_RS0106020
paaK	phenylacetate-CoA ligase	H567_RS0100815	H567_RS0115090
pad-dh	phenylacetaldehyde dehydrogenase
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	H567_RS25900	H567_RS0104770
padD	phenylacetyl-CoA dehydrogenase, PadD subunit
padE	phenylglyoxylate dehydrogenase, gamma subunit	H567_RS0117880	H567_RS0118050
padF	phenylglyoxylate dehydrogenase, delta subunit	H567_RS0121235	H567_RS0121215
padG	phenylglyoxylate dehydrogenase, alpha subunit	H567_RS0121230	H567_RS0121210
padH	phenylglyoxylate dehydrogenase, epsilon subunit
padI	phenylglyoxylate dehydrogenase, beta subunit
PAH	phenylalanine 4-monooxygenase
PCBD	pterin-4-alpha-carbinoalamine dehydratase
pfor	phenylacetaldeyde:ferredoxin oxidoreductase	H567_RS23810	H567_RS27885
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	H567_RS0110730	H567_RS0115465
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit
pimF	6-carboxyhex-2-enoyl-CoA hydratase
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	H567_RS0119820
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	H567_RS0119825
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.