L-phenylalanine catabolism in Actinokineospora bangkokensis 44EHW

Best path

livF, livG, livH, livM, livJ, ARO8, PPDCalpha, PPDCbeta, pad-dh, paaK, 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 (49 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	BJP25_RS06775	BJP25_RS13540
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	BJP25_RS06770	BJP25_RS13545
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	BJP25_RS06760	BJP25_RS13535
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	BJP25_RS06765	BJP25_RS13530
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	BJP25_RS32065	BJP25_RS06755
ARO8	L-phenylalanine transaminase	BJP25_RS00055	BJP25_RS26845
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	BJP25_RS26405	BJP25_RS00495
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	BJP25_RS26410	BJP25_RS00500
pad-dh	phenylacetaldehyde dehydrogenase	BJP25_RS23515	BJP25_RS29000
paaK	phenylacetate-CoA ligase	BJP25_RS14570	BJP25_RS30780
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	BJP25_RS14555
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	BJP25_RS14550
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	BJP25_RS14545
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	BJP25_RS14535
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	BJP25_RS29835	BJP25_RS24615
paaZ1	oxepin-CoA hydrolase	BJP25_RS14560	BJP25_RS29835
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	BJP25_RS14560
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	BJP25_RS14530	BJP25_RS12275
paaF	2,3-dehydroadipyl-CoA hydratase	BJP25_RS21155	BJP25_RS29835
paaH	3-hydroxyadipyl-CoA dehydrogenase	BJP25_RS15590	BJP25_RS21355
paaJ2	3-oxoadipyl-CoA thiolase	BJP25_RS14530	BJP25_RS12275
Alternative steps:
aacS	acetoacetyl-CoA synthetase	BJP25_RS09965	BJP25_RS28365
ARO10	phenylpyruvate decarboxylase
aroP	L-phenylalanine:H+ symporter AroP	BJP25_RS17955
atoA	acetoacetyl-CoA transferase, A subunit	BJP25_RS10040	BJP25_RS12280
atoB	acetyl-CoA C-acetyltransferase	BJP25_RS21275	BJP25_RS14530
atoD	acetoacetyl-CoA transferase, B subunit	BJP25_RS10035	BJP25_RS12285
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	BJP25_RS08285	BJP25_RS30855
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	BJP25_RS24820	BJP25_RS21155
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	BJP25_RS21155	BJP25_RS29835
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	BJP25_RS26255
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	BJP25_RS24700
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	BJP25_RS14560
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	BJP25_RS15595	BJP25_RS23200
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	BJP25_RS21155
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BJP25_RS21155	BJP25_RS29180
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	BJP25_RS15590	BJP25_RS21355
fahA	fumarylacetoacetate hydrolase	BJP25_RS00460	BJP25_RS20880
gcdH	glutaryl-CoA dehydrogenase	BJP25_RS05505	BJP25_RS22655
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase	BJP25_RS00470
HPD	4-hydroxyphenylpyruvate dioxygenase	BJP25_RS29425
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	BJP25_RS25610
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
maiA	maleylacetoacetate isomerase
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	BJP25_RS03635
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	BJP25_RS12355
padI	phenylglyoxylate dehydrogenase, beta subunit
PAH	phenylalanine 4-monooxygenase
PCBD	pterin-4-alpha-carbinoalamine dehydratase	BJP25_RS29650
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	BJP25_RS14530	BJP25_RS18285
pimC	pimeloyl-CoA dehydrogenase, small subunit	BJP25_RS05505	BJP25_RS03200
pimD	pimeloyl-CoA dehydrogenase, large subunit	BJP25_RS08295	BJP25_RS05420
pimF	6-carboxyhex-2-enoyl-CoA hydratase	BJP25_RS03225	BJP25_RS02865
QDPR	6,7-dihydropteridine reductase	BJP25_RS04085

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.