L-phenylalanine catabolism in Verminephrobacter eiseniae EF01-2

Best path

livF, livG, livH, livM, livJ, ARO8, iorAB, 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 (52 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	VEIS_RS14570	VEIS_RS09160
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	VEIS_RS14575	VEIS_RS09155
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	VEIS_RS14585	VEIS_RS09145
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	VEIS_RS14580	VEIS_RS09150
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	VEIS_RS23840	VEIS_RS23860
ARO8	L-phenylalanine transaminase	VEIS_RS08580	VEIS_RS14130
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	VEIS_RS18395	VEIS_RS19805
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	VEIS_RS19100
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	VEIS_RS19105
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	VEIS_RS19110
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	VEIS_RS19120
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	VEIS_RS19085	VEIS_RS20645
paaZ1	oxepin-CoA hydrolase	VEIS_RS18635	VEIS_RS19085
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	VEIS_RS01505	VEIS_RS18480
paaF	2,3-dehydroadipyl-CoA hydratase	VEIS_RS02240	VEIS_RS08860
paaH	3-hydroxyadipyl-CoA dehydrogenase	VEIS_RS24060	VEIS_RS08750
paaJ2	3-oxoadipyl-CoA thiolase	VEIS_RS01505	VEIS_RS18480
Alternative steps:
aacS	acetoacetyl-CoA synthetase	VEIS_RS15465	VEIS_RS01765
ARO10	phenylpyruvate decarboxylase
aroP	L-phenylalanine:H+ symporter AroP	VEIS_RS13795
atoA	acetoacetyl-CoA transferase, A subunit	VEIS_RS12710	VEIS_RS19500
atoB	acetyl-CoA C-acetyltransferase	VEIS_RS18480	VEIS_RS06505
atoD	acetoacetyl-CoA transferase, B subunit	VEIS_RS12705	VEIS_RS19495
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	VEIS_RS19865	VEIS_RS18725
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	VEIS_RS19870	VEIS_RS01100
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	VEIS_RS02240	VEIS_RS08860
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	VEIS_RS19640
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	VEIS_RS11680	VEIS_RS13680
bamI	class II benzoyl-CoA reductase, BamI subunit	VEIS_RS11675	VEIS_RS13675
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	VEIS_RS03605
boxB	benzoyl-CoA epoxidase, subunit B	VEIS_RS03600
boxC	2,3-epoxybenzoyl-CoA dihydrolase	VEIS_RS03595
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	VEIS_RS04310	VEIS_RS01120
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	VEIS_RS18720	VEIS_RS16985
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	VEIS_RS02240	VEIS_RS18720
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	VEIS_RS24060	VEIS_RS08750
fahA	fumarylacetoacetate hydrolase	VEIS_RS04875	VEIS_RS22410
gcdH	glutaryl-CoA dehydrogenase	VEIS_RS08445	VEIS_RS06515
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	VEIS_RS15695
hmgA	homogentisate dioxygenase
HPD	4-hydroxyphenylpyruvate dioxygenase	VEIS_RS10440
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
maiA	maleylacetoacetate isomerase	VEIS_RS18495	VEIS_RS19035
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
paaK	phenylacetate-CoA ligase	VEIS_RS19095	VEIS_RS04295
pad-dh	phenylacetaldehyde dehydrogenase	VEIS_RS17035	VEIS_RS09480
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	VEIS_RS19340
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	VEIS_RS10435
PCBD	pterin-4-alpha-carbinoalamine dehydratase	VEIS_RS01605
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	VEIS_RS24065	VEIS_RS08745
pimC	pimeloyl-CoA dehydrogenase, small subunit	VEIS_RS24050	VEIS_RS10285
pimD	pimeloyl-CoA dehydrogenase, large subunit	VEIS_RS24055	VEIS_RS10280
pimF	6-carboxyhex-2-enoyl-CoA hydratase	VEIS_RS24060	VEIS_RS08750
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	VEIS_RS10880
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	VEIS_RS10875
QDPR	6,7-dihydropteridine reductase	VEIS_RS20330

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.