L-phenylalanine catabolism in Paraburkholderia sp. CCGE1002

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 (53 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	BC1002_RS34535	BC1002_RS29020
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	BC1002_RS34540	BC1002_RS29445
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	BC1002_RS11925	BC1002_RS34550
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	BC1002_RS34545	BC1002_RS11920
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	BC1002_RS00535	BC1002_RS23155
ARO8	L-phenylalanine transaminase	BC1002_RS11170	BC1002_RS33050
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	BC1002_RS00820	BC1002_RS14690
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	BC1002_RS33150
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	BC1002_RS33145
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	BC1002_RS33140	BC1002_RS14645
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	BC1002_RS33130	BC1002_RS14655
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	BC1002_RS13745	BC1002_RS20360
paaZ1	oxepin-CoA hydrolase	BC1002_RS04865	BC1002_RS20360
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	BC1002_RS13740	BC1002_RS33125
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	BC1002_RS17450	BC1002_RS33120
paaF	2,3-dehydroadipyl-CoA hydratase	BC1002_RS13735	BC1002_RS28515
paaH	3-hydroxyadipyl-CoA dehydrogenase	BC1002_RS01910	BC1002_RS09925
paaJ2	3-oxoadipyl-CoA thiolase	BC1002_RS17450	BC1002_RS33120
Alternative steps:
aacS	acetoacetyl-CoA synthetase	BC1002_RS15535	BC1002_RS13690
ARO10	phenylpyruvate decarboxylase
aroP	L-phenylalanine:H+ symporter AroP	BC1002_RS33045	BC1002_RS11820
atoA	acetoacetyl-CoA transferase, A subunit	BC1002_RS10020	BC1002_RS22760
atoB	acetyl-CoA C-acetyltransferase	BC1002_RS07005	BC1002_RS07035
atoD	acetoacetyl-CoA transferase, B subunit	BC1002_RS10015	BC1002_RS22755
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	BC1002_RS18000	BC1002_RS30265
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	BC1002_RS13735	BC1002_RS28515
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	BC1002_RS13735	BC1002_RS28515
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	BC1002_RS19315
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	BC1002_RS04760	BC1002_RS11230
bamI	class II benzoyl-CoA reductase, BamI subunit	BC1002_RS11235	BC1002_RS04765
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	BC1002_RS09860
boxB	benzoyl-CoA epoxidase, subunit B	BC1002_RS09865
boxC	2,3-epoxybenzoyl-CoA dihydrolase	BC1002_RS09870
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	BC1002_RS20990	BC1002_RS00980
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	BC1002_RS20970	BC1002_RS28515
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BC1002_RS13735	BC1002_RS28515
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	BC1002_RS01910	BC1002_RS09925
fahA	fumarylacetoacetate hydrolase	BC1002_RS02710	BC1002_RS01095
gcdH	glutaryl-CoA dehydrogenase	BC1002_RS02685	BC1002_RS20990
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase	BC1002_RS02705	BC1002_RS20860
HPD	4-hydroxyphenylpyruvate dioxygenase	BC1002_RS33040	BC1002_RS14680
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit	BC1002_RS00820
maiA	maleylacetoacetate isomerase	BC1002_RS01505	BC1002_RS14020
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
paaK	phenylacetate-CoA ligase	BC1002_RS13755	BC1002_RS33110
pad-dh	phenylacetaldehyde dehydrogenase	BC1002_RS07840	BC1002_RS16940
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
PAH	phenylalanine 4-monooxygenase	BC1002_RS15680
PCBD	pterin-4-alpha-carbinoalamine dehydratase	BC1002_RS15685	BC1002_RS16175
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	BC1002_RS07325	BC1002_RS20375
pimC	pimeloyl-CoA dehydrogenase, small subunit	BC1002_RS09935	BC1002_RS20365
pimD	pimeloyl-CoA dehydrogenase, large subunit	BC1002_RS04825	BC1002_RS20370
pimF	6-carboxyhex-2-enoyl-CoA hydratase	BC1002_RS07320	BC1002_RS09925
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	BC1002_RS29375	BC1002_RS32875
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	BC1002_RS29370	BC1002_RS32880
QDPR	6,7-dihydropteridine reductase	BC1002_RS31475	BC1002_RS26340

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.