L-phenylalanine catabolism in Desulfitobacterium hafniense DCB-2

Best path

aroP, 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 (37 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
aroP	L-phenylalanine:H+ symporter AroP	DHAF_RS06640	DHAF_RS12190
ARO8	L-phenylalanine transaminase	DHAF_RS14715	DHAF_RS11905
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB
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	DHAF_RS18210	DHAF_RS14270
paaZ1	oxepin-CoA hydrolase	DHAF_RS18210
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	DHAF_RS14275	DHAF_RS03095
paaF	2,3-dehydroadipyl-CoA hydratase	DHAF_RS14270	DHAF_RS18210
paaH	3-hydroxyadipyl-CoA dehydrogenase	DHAF_RS22630	DHAF_RS18220
paaJ2	3-oxoadipyl-CoA thiolase	DHAF_RS14275	DHAF_RS03095
Alternative steps:
aacS	acetoacetyl-CoA synthetase	DHAF_RS18135	DHAF_RS01655
ARO10	phenylpyruvate decarboxylase
atoA	acetoacetyl-CoA transferase, A subunit
atoB	acetyl-CoA C-acetyltransferase	DHAF_RS03095	DHAF_RS14275
atoD	acetoacetyl-CoA transferase, B subunit
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	DHAF_RS13285	DHAF_RS19070
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	DHAF_RS02440	DHAF_RS14270
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	DHAF_RS14270	DHAF_RS18210
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit	DHAF_RS10260
bamD	class II benzoyl-CoA reductase, BamD subunit	DHAF_RS18195	DHAF_RS08520
bamE	class II benzoyl-CoA reductase, BamE subunit
bamF	class II benzoyl-CoA reductase, BamF subunit
bamG	class II benzoyl-CoA reductase, BamG subunit	DHAF_RS06990
bamH	class II benzoyl-CoA reductase, BamH subunit	DHAF_RS06995
bamI	class II benzoyl-CoA reductase, BamI subunit	DHAF_RS18855
bcrA	ATP-dependent benzoyl-CoA reductase, alpha subunit	DHAF_RS05510	DHAF_RS17235
bcrB	ATP-dependent benzoyl-CoA reductase, beta subunit	DHAF_RS17240
bcrC	ATP-dependent benzoyl-CoA reductase, gamma subunit
bcrD	ATP-dependent benzoyl-CoA reductase, delta subunit	DHAF_RS05510	DHAF_RS17235
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	DHAF_RS14315	DHAF_RS13520
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	DHAF_RS14270	DHAF_RS18210
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	DHAF_RS14270	DHAF_RS18210
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	DHAF_RS22630	DHAF_RS18220
fahA	fumarylacetoacetate hydrolase	DHAF_RS15245
gcdH	glutaryl-CoA dehydrogenase	DHAF_RS14305	DHAF_RS14315
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase
HPD	4-hydroxyphenylpyruvate dioxygenase
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	DHAF_RS24525	DHAF_RS01145
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	DHAF_RS24530	DHAF_RS24525
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	DHAF_RS24540
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	DHAF_RS24535
maiA	maleylacetoacetate isomerase
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
paaK	phenylacetate-CoA ligase	DHAF_RS17250	DHAF_RS22940
pad-dh	phenylacetaldehyde dehydrogenase	DHAF_RS10840	DHAF_RS13220
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	DHAF_RS21090	DHAF_RS08135
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	DHAF_RS15720	DHAF_RS04440
padI	phenylglyoxylate dehydrogenase, beta subunit
PAH	phenylalanine 4-monooxygenase
PCBD	pterin-4-alpha-carbinoalamine dehydratase
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	DHAF_RS22625	DHAF_RS03095
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit
pimF	6-carboxyhex-2-enoyl-CoA hydratase
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit
PPDCbeta	phenylpyruvate decarboxylase, beta subunit
QDPR	6,7-dihydropteridine reductase	DHAF_RS16670

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.