L-phenylalanine catabolism in Saccharomonospora marina XMU15

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 (48 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
aroP	L-phenylalanine:H+ symporter AroP
ARO8	L-phenylalanine transaminase	SACMADRAFT_RS03235	SACMADRAFT_RS28295
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	SACMADRAFT_RS27870	SACMADRAFT_RS18020
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	SACMADRAFT_RS27875	SACMADRAFT_RS12840
pad-dh	phenylacetaldehyde dehydrogenase	SACMADRAFT_RS19485	SACMADRAFT_RS26445
paaK	phenylacetate-CoA ligase	SACMADRAFT_RS23775	SACMADRAFT_RS10280
paaA	phenylacetyl-CoA 1,2-epoxidase, subunit A	SACMADRAFT_RS23760
paaB	phenylacetyl-CoA 1,2-epoxidase, subunit B	SACMADRAFT_RS23755
paaC	phenylacetyl-CoA 1,2-epoxidase, subunit C	SACMADRAFT_RS23750
paaE	phenylacetyl-CoA 1,2-epoxidase, subunit E	SACMADRAFT_RS23740	SACMADRAFT_RS10920
paaG	1,2-epoxyphenylacetyl-CoA isomerase / 2-(oxepinyl)acetyl-CoA isomerase / didehydroadipyl-CoA isomerase	SACMADRAFT_RS04595	SACMADRAFT_RS23005
paaZ1	oxepin-CoA hydrolase	SACMADRAFT_RS23765	SACMADRAFT_RS10990
paaZ2	3-oxo-5,6-didehydrosuberyl-CoA semialdehyde dehydrogenase	SACMADRAFT_RS23765
paaJ1	3-oxo-5,6-dehydrosuberyl-CoA thiolase	SACMADRAFT_RS08505	SACMADRAFT_RS17870
paaF	2,3-dehydroadipyl-CoA hydratase	SACMADRAFT_RS19140	SACMADRAFT_RS14875
paaH	3-hydroxyadipyl-CoA dehydrogenase	SACMADRAFT_RS27015	SACMADRAFT_RS12380
paaJ2	3-oxoadipyl-CoA thiolase	SACMADRAFT_RS08505	SACMADRAFT_RS17870
Alternative steps:
aacS	acetoacetyl-CoA synthetase	SACMADRAFT_RS01985	SACMADRAFT_RS23315
ARO10	phenylpyruvate decarboxylase
atoA	acetoacetyl-CoA transferase, A subunit	SACMADRAFT_RS19575
atoB	acetyl-CoA C-acetyltransferase	SACMADRAFT_RS19295	SACMADRAFT_RS10145
atoD	acetoacetyl-CoA transferase, B subunit	SACMADRAFT_RS19570
badH	2-hydroxy-cyclohexanecarboxyl-CoA dehydrogenase	SACMADRAFT_RS15760	SACMADRAFT_RS08725
badI	2-ketocyclohexanecarboxyl-CoA hydrolase	SACMADRAFT_RS02710	SACMADRAFT_RS26285
badK	cyclohex-1-ene-1-carboxyl-CoA hydratase	SACMADRAFT_RS19140	SACMADRAFT_RS14875
bamB	class II benzoyl-CoA reductase, BamB subunit
bamC	class II benzoyl-CoA reductase, BamC subunit
bamD	class II benzoyl-CoA reductase, BamD subunit	SACMADRAFT_RS09390	SACMADRAFT_RS27655
bamE	class II benzoyl-CoA reductase, BamE subunit
bamF	class II benzoyl-CoA reductase, BamF subunit
bamG	class II benzoyl-CoA reductase, BamG subunit	SACMADRAFT_RS25255
bamH	class II benzoyl-CoA reductase, BamH subunit	SACMADRAFT_RS25260	SACMADRAFT_RS09545
bamI	class II benzoyl-CoA reductase, BamI subunit	SACMADRAFT_RS25265
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	SACMADRAFT_RS05810
boxC	2,3-epoxybenzoyl-CoA dihydrolase	SACMADRAFT_RS05805
boxD	3,4-dehydroadipyl-CoA semialdehyde dehydrogenase	SACMADRAFT_RS23765	SACMADRAFT_RS26775
Ch1CoA	cyclohex-1-ene-1-carbonyl-CoA dehydrogenase	SACMADRAFT_RS04405	SACMADRAFT_RS23115
dch	cyclohexa-1,5-diene-1-carboxyl-CoA hydratase	SACMADRAFT_RS26285	SACMADRAFT_RS19140
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	SACMADRAFT_RS19140	SACMADRAFT_RS21080
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	SACMADRAFT_RS27015	SACMADRAFT_RS12380
fahA	fumarylacetoacetate hydrolase	SACMADRAFT_RS12985	SACMADRAFT_RS06235
gcdH	glutaryl-CoA dehydrogenase	SACMADRAFT_RS06025	SACMADRAFT_RS21150
had	6-hydroxycyclohex-1-ene-1-carbonyl-CoA dehydrogenase
hmgA	homogentisate dioxygenase	SACMADRAFT_RS12975
HPD	4-hydroxyphenylpyruvate dioxygenase	SACMADRAFT_RS21810
iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB
iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit
livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	SACMADRAFT_RS27835	SACMADRAFT_RS12295
livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	SACMADRAFT_RS27840	SACMADRAFT_RS24980
livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	SACMADRAFT_RS27850	SACMADRAFT_RS19805
livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK
livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	SACMADRAFT_RS27855	SACMADRAFT_RS12310
maiA	maleylacetoacetate isomerase
oah	6-oxocyclohex-1-ene-1-carbonyl-CoA hydratase
padB	phenylacetyl-CoA dehydrogenase, PadB subunit
padC	phenylacetyl-CoA dehydrogenase, PadC subunit	SACMADRAFT_RS15560
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	SACMADRAFT_RS21585
pfor	phenylacetaldeyde:ferredoxin oxidoreductase
pimB	3-oxopimeloyl-CoA:CoA acetyltransferase	SACMADRAFT_RS17870	SACMADRAFT_RS10145
pimC	pimeloyl-CoA dehydrogenase, small subunit	SACMADRAFT_RS10105	SACMADRAFT_RS26325
pimD	pimeloyl-CoA dehydrogenase, large subunit	SACMADRAFT_RS10130	SACMADRAFT_RS15780
pimF	6-carboxyhex-2-enoyl-CoA hydratase	SACMADRAFT_RS05795
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.