L-phenylalanine catabolism in Rhizobium leguminosarum WSM1325

Best path

livF, livG, livH, livM, livJ, PAH, PCBD, QDPR, HPD, hmgA, maiA, fahA, aacS, 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 (39 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	RLEG_RS16400	RLEG_RS30575
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	RLEG_RS16405	RLEG_RS27560
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	RLEG_RS16415	RLEG_RS23810
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	RLEG_RS16410	RLEG_RS30565
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	RLEG_RS16390	RLEG_RS15300
PAH	phenylalanine 4-monooxygenase	RLEG_RS07435
PCBD	pterin-4-alpha-carbinoalamine dehydratase	RLEG_RS20050
QDPR	6,7-dihydropteridine reductase	RLEG_RS27200
HPD	4-hydroxyphenylpyruvate dioxygenase	RLEG_RS07450	RLEG_RS29310
hmgA	homogentisate dioxygenase	RLEG_RS07455
maiA	maleylacetoacetate isomerase	RLEG_RS07465	RLEG_RS11230
fahA	fumarylacetoacetate hydrolase	RLEG_RS07460	RLEG_RS21170
aacS	acetoacetyl-CoA synthetase	RLEG_RS02080	RLEG_RS03060
atoB	acetyl-CoA C-acetyltransferase	RLEG_RS20540	RLEG_RS35140
Alternative steps:
ARO10	phenylpyruvate decarboxylase
ARO8	L-phenylalanine transaminase	RLEG_RS14800	RLEG_RS17220
aroP	L-phenylalanine:H+ symporter AroP
atoA	acetoacetyl-CoA transferase, A subunit	RLEG_RS27925
atoD	acetoacetyl-CoA transferase, B subunit	RLEG_RS27920
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	RLEG_RS33500	RLEG_RS20535
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	RLEG_RS23030	RLEG_RS26045
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	RLEG_RS23030	RLEG_RS26045
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	RLEG_RS19430	RLEG_RS06695
bamI	class II benzoyl-CoA reductase, BamI subunit
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
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	RLEG_RS35135	RLEG_RS35160
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	RLEG_RS23030	RLEG_RS34755
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	RLEG_RS23030	RLEG_RS26045
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	RLEG_RS01235	RLEG_RS19090
gcdH	glutaryl-CoA dehydrogenase	RLEG_RS27635	RLEG_RS35135
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
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	RLEG_RS24055
paaF	2,3-dehydroadipyl-CoA hydratase	RLEG_RS23030	RLEG_RS26045
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	RLEG_RS26045	RLEG_RS23030
paaH	3-hydroxyadipyl-CoA dehydrogenase	RLEG_RS01235	RLEG_RS19090
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	RLEG_RS27915	RLEG_RS20540
paaJ2	3-oxoadipyl-CoA thiolase	RLEG_RS27915	RLEG_RS20540
paaK	phenylacetate-CoA ligase	RLEG_RS23870
paaZ1	oxepin-CoA hydrolase	RLEG_RS23030	RLEG_RS26045
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase
pad-dh	phenylacetaldehyde dehydrogenase	RLEG_RS04395	RLEG_RS18780
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit
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
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	RLEG_RS20540	RLEG_RS27915
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit
pimF	6-carboxyhex-2-enoyl-CoA hydratase	RLEG_RS01235
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	RLEG_RS35130
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	RLEG_RS35125	RLEG_RS08915

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.