L-phenylalanine catabolism in Methylobacterium nodulans ORS 2060

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 (53 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	MNOD_RS08395	MNOD_RS05610
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	MNOD_RS08405	MNOD_RS01650
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	MNOD_RS08415	MNOD_RS31080
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	MNOD_RS08410	MNOD_RS05615
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	MNOD_RS08385	MNOD_RS14755
ARO8	L-phenylalanine transaminase	MNOD_RS09470	MNOD_RS37310
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	MNOD_RS15970	MNOD_RS30740
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	MNOD_RS15975	MNOD_RS30745
pad-dh	phenylacetaldehyde dehydrogenase	MNOD_RS35765	MNOD_RS07620
paaK	phenylacetate-CoA ligase	MNOD_RS15925	MNOD_RS26145
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	MNOD_RS15870	MNOD_RS34030
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	MNOD_RS15865	MNOD_RS34025
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	MNOD_RS15860	MNOD_RS34020
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	MNOD_RS15850	MNOD_RS34010
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	MNOD_RS26135	MNOD_RS15905
paaZ1	oxepin-CoA hydrolase	MNOD_RS15885	MNOD_RS26135
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	MNOD_RS15885	MNOD_RS15900
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	MNOD_RS15895	MNOD_RS13390
paaF	2,3-dehydroadipyl-CoA hydratase	MNOD_RS00720	MNOD_RS18785
paaH	3-hydroxyadipyl-CoA dehydrogenase	MNOD_RS15890	MNOD_RS24770
paaJ2	3-oxoadipyl-CoA thiolase	MNOD_RS15895	MNOD_RS13390
Alternative steps:
aacS	acetoacetyl-CoA synthetase	MNOD_RS01420	MNOD_RS34300
ARO10	phenylpyruvate decarboxylase
aroP	L-phenylalanine:H+ symporter AroP	MNOD_RS23565	MNOD_RS04385
atoA	acetoacetyl-CoA transferase, A subunit	MNOD_RS30055	MNOD_RS10965
atoB	acetyl-CoA C-acetyltransferase	MNOD_RS27980	MNOD_RS18795
atoD	acetoacetyl-CoA transferase, B subunit	MNOD_RS30060	MNOD_RS10970
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	MNOD_RS42370	MNOD_RS16440
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	MNOD_RS00720	MNOD_RS26135
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	MNOD_RS00720	MNOD_RS18785
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	MNOD_RS16065
bamE	class II benzoyl-CoA reductase, BamE subunit
bamF	class II benzoyl-CoA reductase, BamF subunit
bamG	class II benzoyl-CoA reductase, BamG subunit	MNOD_RS01260
bamH	class II benzoyl-CoA reductase, BamH subunit	MNOD_RS01255	MNOD_RS24700
bamI	class II benzoyl-CoA reductase, BamI subunit	MNOD_RS01250
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	MNOD_RS15885
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	MNOD_RS17160	MNOD_RS10500
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	MNOD_RS00720	MNOD_RS18785
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	MNOD_RS00720	MNOD_RS18785
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	MNOD_RS15890	MNOD_RS24770
fahA	fumarylacetoacetate hydrolase	MNOD_RS05755	MNOD_RS13590
gcdH	glutaryl-CoA dehydrogenase	MNOD_RS06130	MNOD_RS01425
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase	MNOD_RS05760
HPD	4-hydroxyphenylpyruvate dioxygenase	MNOD_RS00570
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	MNOD_RS01415
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit	MNOD_RS01415
maiA	maleylacetoacetate isomerase	MNOD_RS05750	MNOD_RS37420
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase	MNOD_RS15905
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	MNOD_RS24960
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	MNOD_RS37695	MNOD_RS28240
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	MNOD_RS25760	MNOD_RS15895
pimC	pimeloyl-CoA dehydrogenase, small subunit	MNOD_RS25745
pimD	pimeloyl-CoA dehydrogenase, large subunit	MNOD_RS25750	MNOD_RS32085
pimF	6-carboxyhex-2-enoyl-CoA hydratase	MNOD_RS25755	MNOD_RS15890
QDPR	6,7-dihydropteridine reductase	MNOD_RS10295	MNOD_RS26835

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.