L-phenylalanine catabolism in Azospirillum humicireducens SgZ-5

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)	A6A40_RS13375	A6A40_RS21795
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	A6A40_RS13380	A6A40_RS29810
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	A6A40_RS13390	A6A40_RS09880
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	A6A40_RS13385	A6A40_RS22595
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	A6A40_RS30135	A6A40_RS13365
ARO8	L-phenylalanine transaminase	A6A40_RS29525	A6A40_RS29075
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	A6A40_RS06170
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	A6A40_RS26635
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	A6A40_RS26630
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	A6A40_RS26625
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	A6A40_RS26615
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	A6A40_RS26605	A6A40_RS28850
paaZ1	oxepin-CoA hydrolase	A6A40_RS20190	A6A40_RS07490
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	A6A40_RS26610
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	A6A40_RS25550	A6A40_RS26590
paaF	2,3-dehydroadipyl-CoA hydratase	A6A40_RS14715	A6A40_RS26605
paaH	3-hydroxyadipyl-CoA dehydrogenase	A6A40_RS26600	A6A40_RS13055
paaJ2	3-oxoadipyl-CoA thiolase	A6A40_RS25550	A6A40_RS26590
Alternative steps:
aacS	acetoacetyl-CoA synthetase	A6A40_RS05525	A6A40_RS15700
ARO10	phenylpyruvate decarboxylase
aroP	L-phenylalanine:H+ symporter AroP
atoA	acetoacetyl-CoA transferase, A subunit	A6A40_RS26060	A6A40_RS22045
atoB	acetyl-CoA C-acetyltransferase	A6A40_RS09435	A6A40_RS28855
atoD	acetoacetyl-CoA transferase, B subunit	A6A40_RS26065	A6A40_RS22040
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	A6A40_RS20625	A6A40_RS09430
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	A6A40_RS14715	A6A40_RS19640
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	A6A40_RS14715	A6A40_RS26605
bamB	class II benzoyl-CoA reductase, BamB subunit	A6A40_RS15325
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	A6A40_RS18285
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	A6A40_RS19425	A6A40_RS28670
bamI	class II benzoyl-CoA reductase, BamI subunit	A6A40_RS19420
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	A6A40_RS19630	A6A40_RS25755
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	A6A40_RS14715	A6A40_RS07510
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	A6A40_RS14715	A6A40_RS26600
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	A6A40_RS13055	A6A40_RS28460
fahA	fumarylacetoacetate hydrolase	A6A40_RS10245	A6A40_RS22305
gcdH	glutaryl-CoA dehydrogenase	A6A40_RS26290	A6A40_RS19620
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase	A6A40_RS04025
hmgA	homogentisate dioxygenase	A6A40_RS25790	A6A40_RS10250
HPD	4-hydroxyphenylpyruvate dioxygenase	A6A40_RS27170	A6A40_RS18975
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
maiA	maleylacetoacetate isomerase	A6A40_RS17345	A6A40_RS10190
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
paaK	phenylacetate-CoA ligase	A6A40_RS26585	A6A40_RS18605
pad-dh	phenylacetaldehyde dehydrogenase	A6A40_RS29725	A6A40_RS13560
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	A6A40_RS02710
padD	phenylacetyl-CoA dehydrogenase, PadD subunit
padE	phenylglyoxylate dehydrogenase, gamma subunit	A6A40_RS22215
padF	phenylglyoxylate dehydrogenase, delta subunit
padG	phenylglyoxylate dehydrogenase, alpha subunit	A6A40_RS22220
padH	phenylglyoxylate dehydrogenase, epsilon subunit
padI	phenylglyoxylate dehydrogenase, beta subunit	A6A40_RS22225
PAH	phenylalanine 4-monooxygenase
PCBD	pterin-4-alpha-carbinoalamine dehydratase	A6A40_RS02820	A6A40_RS11640
pfor	phenylacetaldeyde:ferredoxin oxidoreductase	A6A40_RS15325
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	A6A40_RS28855	A6A40_RS27600
pimC	pimeloyl-CoA dehydrogenase, small subunit	A6A40_RS20230
pimD	pimeloyl-CoA dehydrogenase, large subunit	A6A40_RS19620
pimF	6-carboxyhex-2-enoyl-CoA hydratase	A6A40_RS28460
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	A6A40_RS03065	A6A40_RS28475
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	A6A40_RS03060	A6A40_RS28470
QDPR	6,7-dihydropteridine reductase	A6A40_RS13300

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.