L-phenylalanine catabolism in Streptacidiphilus oryzae TH49

Best path

aroP, 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 (54 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
aroP	L-phenylalanine:H+ symporter AroP	BS73_RS16535	BS73_RS25710
ARO8	L-phenylalanine transaminase	BS73_RS22570	BS73_RS16820
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	BS73_RS19365	BS73_RS19265
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	BS73_RS19370	BS73_RS19260
pad-dh	phenylacetaldehyde dehydrogenase	BS73_RS27490	BS73_RS24675
paaK	phenylacetate-CoA ligase	BS73_RS02650	BS73_RS11295
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	BS73_RS31860
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	BS73_RS31855
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	BS73_RS38505
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	BS73_RS31840
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	BS73_RS02310	BS73_RS32220
paaZ1	oxepin-CoA hydrolase	BS73_RS05650	BS73_RS00955
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	BS73_RS30630	BS73_RS12600
paaF	2,3-dehydroadipyl-CoA hydratase	BS73_RS14910	BS73_RS20300
paaH	3-hydroxyadipyl-CoA dehydrogenase	BS73_RS08975	BS73_RS07230
paaJ2	3-oxoadipyl-CoA thiolase	BS73_RS30630	BS73_RS12600
Alternative steps:
aacS	acetoacetyl-CoA synthetase	BS73_RS34115	BS73_RS06735
ARO10	phenylpyruvate decarboxylase	BS73_RS33080
atoA	acetoacetyl-CoA transferase, A subunit	BS73_RS10025
atoB	acetyl-CoA C-acetyltransferase	BS73_RS10365	BS73_RS08675
atoD	acetoacetyl-CoA transferase, B subunit	BS73_RS10020
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	BS73_RS03225	BS73_RS09090
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	BS73_RS32220	BS73_RS07070
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	BS73_RS14910	BS73_RS05650
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	BS73_RS19015
bamE	class II benzoyl-CoA reductase, BamE subunit
bamF	class II benzoyl-CoA reductase, BamF subunit
bamG	class II benzoyl-CoA reductase, BamG subunit	BS73_RS32425
bamH	class II benzoyl-CoA reductase, BamH subunit	BS73_RS32420	BS73_RS21765
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	BS73_RS07420
boxC	2,3-epoxybenzoyl-CoA dihydrolase	BS73_RS07415
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	BS73_RS23895	BS73_RS08225
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	BS73_RS00915	BS73_RS14910
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BS73_RS14910	BS73_RS05650
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	BS73_RS08975	BS73_RS07230
fahA	fumarylacetoacetate hydrolase	BS73_RS09715	BS73_RS30775
gcdH	glutaryl-CoA dehydrogenase	BS73_RS32915	BS73_RS25270
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase	BS73_RS09710
HPD	4-hydroxyphenylpyruvate dioxygenase	BS73_RS24460
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	BS73_RS06630
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	BS73_RS29110	BS73_RS13620
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	BS73_RS29115	BS73_RS00335
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	BS73_RS29125	BS73_RS13625
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	BS73_RS29120
maiA	maleylacetoacetate isomerase
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	BS73_RS32220
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	BS73_RS10710
padD	phenylacetyl-CoA dehydrogenase, PadD subunit
padE	phenylglyoxylate dehydrogenase, gamma subunit	BS73_RS06410
padF	phenylglyoxylate dehydrogenase, delta subunit
padG	phenylglyoxylate dehydrogenase, alpha subunit	BS73_RS06405
padH	phenylglyoxylate dehydrogenase, epsilon subunit	BS73_RS33040
padI	phenylglyoxylate dehydrogenase, beta subunit	BS73_RS06400
PAH	phenylalanine 4-monooxygenase
PCBD	pterin-4-alpha-carbinoalamine dehydratase	BS73_RS11640
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	BS73_RS15085	BS73_RS30630
pimC	pimeloyl-CoA dehydrogenase, small subunit	BS73_RS07080	BS73_RS00880
pimD	pimeloyl-CoA dehydrogenase, large subunit	BS73_RS07085	BS73_RS33675
pimF	6-carboxyhex-2-enoyl-CoA hydratase	BS73_RS06375	BS73_RS32280
QDPR	6,7-dihydropteridine reductase	BS73_RS18030

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.