L-phenylalanine catabolism in Microvirga lotononidis WSM3557

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 (45 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	MICLODRAFT_RS30925	MICLODRAFT_RS27000
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	MICLODRAFT_RS30920	MICLODRAFT_RS27005
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	MICLODRAFT_RS30910	MICLODRAFT_RS27015
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	MICLODRAFT_RS30915	MICLODRAFT_RS27010
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	MICLODRAFT_RS30935	MICLODRAFT_RS25195
ARO8	L-phenylalanine transaminase	MICLODRAFT_RS32165	MICLODRAFT_RS19120
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	MICLODRAFT_RS27100	MICLODRAFT_RS18635
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	MICLODRAFT_RS27070
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	MICLODRAFT_RS27065
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	MICLODRAFT_RS27060
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	MICLODRAFT_RS27050
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	MICLODRAFT_RS27025	MICLODRAFT_RS29860
paaZ1	oxepin-CoA hydrolase	MICLODRAFT_RS27080	MICLODRAFT_RS27025
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	MICLODRAFT_RS27080
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	MICLODRAFT_RS10820	MICLODRAFT_RS27925
paaF	2,3-dehydroadipyl-CoA hydratase	MICLODRAFT_RS07440	MICLODRAFT_RS27025
paaH	3-hydroxyadipyl-CoA dehydrogenase	MICLODRAFT_RS27085	MICLODRAFT_RS11370
paaJ2	3-oxoadipyl-CoA thiolase	MICLODRAFT_RS10820	MICLODRAFT_RS27925
Alternative steps:
aacS	acetoacetyl-CoA synthetase	MICLODRAFT_RS32190	MICLODRAFT_RS22300
ARO10	phenylpyruvate decarboxylase
aroP	L-phenylalanine:H+ symporter AroP
atoA	acetoacetyl-CoA transferase, A subunit	MICLODRAFT_RS23795	MICLODRAFT_RS09110
atoB	acetyl-CoA C-acetyltransferase	MICLODRAFT_RS27925	MICLODRAFT_RS10820
atoD	acetoacetyl-CoA transferase, B subunit	MICLODRAFT_RS23800	MICLODRAFT_RS09115
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	MICLODRAFT_RS23635	MICLODRAFT_RS15835
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	MICLODRAFT_RS27025	MICLODRAFT_RS07440
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	MICLODRAFT_RS07440	MICLODRAFT_RS27025
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit
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	MICLODRAFT_RS00980	MICLODRAFT_RS10260
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	MICLODRAFT_RS27080
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	MICLODRAFT_RS17470	MICLODRAFT_RS25365
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	MICLODRAFT_RS03885	MICLODRAFT_RS29860
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	MICLODRAFT_RS07440	MICLODRAFT_RS11370
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	MICLODRAFT_RS27085	MICLODRAFT_RS11370
fahA	fumarylacetoacetate hydrolase	MICLODRAFT_RS26530	MICLODRAFT_RS23545
gcdH	glutaryl-CoA dehydrogenase	MICLODRAFT_RS17745	MICLODRAFT_RS25365
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase	MICLODRAFT_RS26535
HPD	4-hydroxyphenylpyruvate dioxygenase	MICLODRAFT_RS23565	MICLODRAFT_RS32345
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
maiA	maleylacetoacetate isomerase	MICLODRAFT_RS26525	MICLODRAFT_RS23560
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	MICLODRAFT_RS27025
paaK	phenylacetate-CoA ligase	MICLODRAFT_RS27035	MICLODRAFT_RS24130
pad-dh	phenylacetaldehyde dehydrogenase	MICLODRAFT_RS03140	MICLODRAFT_RS25285
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
PCBD	pterin-4-alpha-carbinoalamine dehydratase	MICLODRAFT_RS29175
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	MICLODRAFT_RS27925	MICLODRAFT_RS10820
pimC	pimeloyl-CoA dehydrogenase, small subunit
pimD	pimeloyl-CoA dehydrogenase, large subunit	MICLODRAFT_RS25365
pimF	6-carboxyhex-2-enoyl-CoA hydratase	MICLODRAFT_RS27085	MICLODRAFT_RS11370
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	MICLODRAFT_RS26750
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	MICLODRAFT_RS26745	MICLODRAFT_RS10540
QDPR	6,7-dihydropteridine reductase

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.