L-phenylalanine catabolism in Desulfacinum hydrothermale DSM 13146

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 (44 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	B9A12_RS02930	B9A12_RS14615
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	B9A12_RS01565	B9A12_RS05165
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	B9A12_RS14630	B9A12_RS02915
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	B9A12_RS14625	B9A12_RS00035
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	B9A12_RS14635	B9A12_RS00020
ARO8	L-phenylalanine transaminase	B9A12_RS02895	B9A12_RS04135
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit	B9A12_RS05180	B9A12_RS01865
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit	B9A12_RS05185	B9A12_RS01860
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	B9A12_RS01110	B9A12_RS11510
paaZ1	oxepin-CoA hydrolase	B9A12_RS01110	B9A12_RS11510
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	B9A12_RS12580	B9A12_RS06945
paaF	2,3-dehydroadipyl-CoA hydratase	B9A12_RS12585	B9A12_RS11510
paaH	3-hydroxyadipyl-CoA dehydrogenase	B9A12_RS06950	B9A12_RS01205
paaJ2	3-oxoadipyl-CoA thiolase	B9A12_RS12580	B9A12_RS06945
Alternative steps:
aacS	acetoacetyl-CoA synthetase	B9A12_RS07840	B9A12_RS03555
ARO10	phenylpyruvate decarboxylase
aroP	L-phenylalanine:H+ symporter AroP
atoA	acetoacetyl-CoA transferase, A subunit
atoB	acetyl-CoA C-acetyltransferase	B9A12_RS12580	B9A12_RS02380
atoD	acetoacetyl-CoA transferase, B subunit
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	B9A12_RS03625	B9A12_RS01145
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	B9A12_RS12585	B9A12_RS11510
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	B9A12_RS12585	B9A12_RS11510
bamB	class II benzoyl-CoA reductase, BamB subunit	B9A12_RS06550
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	B9A12_RS10120
bamE	class II benzoyl-CoA reductase, BamE subunit	B9A12_RS09240	B9A12_RS12405
bamF	class II benzoyl-CoA reductase, BamF subunit	B9A12_RS13545	B9A12_RS04865
bamG	class II benzoyl-CoA reductase, BamG subunit	B9A12_RS11285	B9A12_RS04415
bamH	class II benzoyl-CoA reductase, BamH subunit	B9A12_RS11280	B9A12_RS04415
bamI	class II benzoyl-CoA reductase, BamI subunit	B9A12_RS07085	B9A12_RS14730
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	B9A12_RS09365	B9A12_RS07565
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	B9A12_RS07565	B9A12_RS09365
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	B9A12_RS03610	B9A12_RS12590
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	B9A12_RS12585	B9A12_RS11510
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	B9A12_RS12585	B9A12_RS11510
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	B9A12_RS06950	B9A12_RS01205
fahA	fumarylacetoacetate hydrolase
gcdH	glutaryl-CoA dehydrogenase	B9A12_RS12590	B9A12_RS03700
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
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
paaK	phenylacetate-CoA ligase	B9A12_RS01540	B9A12_RS13255
pad-dh	phenylacetaldehyde dehydrogenase	B9A12_RS10445	B9A12_RS14640
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	B9A12_RS08245	B9A12_RS07105
padD	phenylacetyl-CoA dehydrogenase, PadD subunit
padE	phenylglyoxylate dehydrogenase, gamma subunit	B9A12_RS08445	B9A12_RS02515
padF	phenylglyoxylate dehydrogenase, delta subunit	B9A12_RS08440
padG	phenylglyoxylate dehydrogenase, alpha subunit	B9A12_RS08435	B9A12_RS03515
padH	phenylglyoxylate dehydrogenase, epsilon subunit
padI	phenylglyoxylate dehydrogenase, beta subunit	B9A12_RS08430	B9A12_RS02530
PAH	phenylalanine 4-monooxygenase
PCBD	pterin-4-alpha-carbinoalamine dehydratase
pfor	phenylacetaldeyde:ferredoxin oxidoreductase	B9A12_RS06550	B9A12_RS15495
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	B9A12_RS12580	B9A12_RS06945
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit	B9A12_RS01155
pimF	6-carboxyhex-2-enoyl-CoA hydratase	B9A12_RS10305
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit
PPDCbeta	phenylpyruvate decarboxylase, beta subunit
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.