L-phenylalanine catabolism in Paraburkholderia phymatum STM815

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 (54 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	BPHY_RS02970	BPHY_RS15485
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	BPHY_RS02965	BPHY_RS15490
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	BPHY_RS02955	BPHY_RS15515
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	BPHY_RS02960
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	BPHY_RS00550	BPHY_RS02950
ARO8	L-phenylalanine transaminase	BPHY_RS03740	BPHY_RS27225
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	BPHY_RS00710	BPHY_RS14615
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	BPHY_RS14560
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	BPHY_RS14565
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	BPHY_RS14570
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	BPHY_RS14580	BPHY_RS20285
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	BPHY_RS13670	BPHY_RS20510
paaZ1	oxepin-CoA hydrolase	BPHY_RS10120	BPHY_RS13670
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	BPHY_RS13660
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	BPHY_RS13665	BPHY_RS19030
paaF	2,3-dehydroadipyl-CoA hydratase	BPHY_RS13655	BPHY_RS10120
paaH	3-hydroxyadipyl-CoA dehydrogenase	BPHY_RS01920	BPHY_RS35840
paaJ2	3-oxoadipyl-CoA thiolase	BPHY_RS19030	BPHY_RS13665
Alternative steps:
aacS	acetoacetyl-CoA synthetase	BPHY_RS15410	BPHY_RS34785
ARO10	phenylpyruvate decarboxylase	BPHY_RS30940
aroP	L-phenylalanine:H+ symporter AroP	BPHY_RS03010	BPHY_RS32965
atoA	acetoacetyl-CoA transferase, A subunit	BPHY_RS07975	BPHY_RS22420
atoB	acetyl-CoA C-acetyltransferase	BPHY_RS04915	BPHY_RS04940
atoD	acetoacetyl-CoA transferase, B subunit	BPHY_RS07970	BPHY_RS22425
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	BPHY_RS20500	BPHY_RS13270
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	BPHY_RS13655	BPHY_RS03820
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	BPHY_RS13655	BPHY_RS24290
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	BPHY_RS29790	BPHY_RS16730
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	BPHY_RS03670	BPHY_RS10220
bamI	class II benzoyl-CoA reductase, BamI subunit	BPHY_RS03665
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	BPHY_RS07840
boxB	benzoyl-CoA epoxidase, subunit B	BPHY_RS07845
boxC	2,3-epoxybenzoyl-CoA dihydrolase	BPHY_RS07850
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	BPHY_RS25695	BPHY_RS00875
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	BPHY_RS24290	BPHY_RS33205
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BPHY_RS13655	BPHY_RS24290
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	BPHY_RS01920	BPHY_RS35840
fahA	fumarylacetoacetate hydrolase	BPHY_RS12345	BPHY_RS00980
gcdH	glutaryl-CoA dehydrogenase	BPHY_RS12365	BPHY_RS18015
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase	BPHY_RS12350
HPD	4-hydroxyphenylpyruvate dioxygenase	BPHY_RS14605	BPHY_RS19615
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit	BPHY_RS00710
maiA	maleylacetoacetate isomerase	BPHY_RS01515	BPHY_RS21695
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
paaK	phenylacetate-CoA ligase	BPHY_RS13680	BPHY_RS29050
pad-dh	phenylacetaldehyde dehydrogenase	BPHY_RS19265	BPHY_RS23615
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	BPHY_RS30955
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
PCBD	pterin-4-alpha-carbinoalamine dehydratase	BPHY_RS32265
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	BPHY_RS05230	BPHY_RS01925
pimC	pimeloyl-CoA dehydrogenase, small subunit	BPHY_RS10155
pimD	pimeloyl-CoA dehydrogenase, large subunit	BPHY_RS10160	BPHY_RS18015
pimF	6-carboxyhex-2-enoyl-CoA hydratase	BPHY_RS05220	BPHY_RS35840
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	BPHY_RS30325
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	BPHY_RS30330	BPHY_RS34910
QDPR	6,7-dihydropteridine reductase	BPHY_RS20285	BPHY_RS27875

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.