GapMind for catabolism of small carbon sources


Definition of L-phenylalanine catabolism

As text, or see rules and steps

# Phenylalanine utilization in GapMind is based on MetaCyc pathway
# L-phenylalanine degradation I (aerobic, via tyrosine, metacyc:PHENYLALANINE-DEG1-PWY),
# pathway II (anaerobic, via phenylacetaldehyde dehydrogenase, metacyc:ANAPHENOXI-PWY),
# 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.)

# In E. coli, the ABC transporter livFGHMJ or livFGHMK transports phenylalanine.
# livJ and livK are alternate substrate binding proteins that are similar to each other.
# A related system in Pseudomonas fluorescens FW300-N2E2 is also important for phenylalanine utlization:
#   Pf6N2E2_2921 = livK = A0A160A0J6; Pf6N2E2_2923 = livH = A0A0D9B2B6; Pf6N2E2_2924 = livM = A0A159ZYE0;
#    Pf6N2E2_2925 = livG = A0A159ZWS6; Pf6N2E2_2926 = livF = A0A159ZWL6).
# Ignored the orthologs in Pseudomonas aeruginosa (the bra system), which transports various
#   amino acids and might transport phenylalanine.
# A related system in Acidovorax sp. GW101-3H11 also transports phenylalanine:
#   LivF = Ac3H11_1692 (A0A165KC78), LivG = Ac3H11_1693 (A0A165KC86),
#   LivJ = Ac3H11_2396 (A0A165KTD4; not near the other components, but cofit),
#   LivH = Ac3H11_1695 (A0A165KC95), LivM = Ac3H11_1694 (A0A165KER0).

livF	L-phenylalanine ABC transporter, ATPase component 1 (LivF)	curated:CharProtDB::CH_003736	uniprot:A0A159ZWL6	ignore:TCDB::P21630	uniprot:A0A165KC78

livG	L-phenylalanine ABC transporter, ATPase component 2 (LivG)	curated:TCDB::P0A9S7	uniprot:A0A159ZWS6	ignore:TCDB::P21629	uniprot:A0A165KC86

livH	L-phenylalanine ABC transporter, permease component 1 (LivH)	curated:ecocyc::LIVH-MONOMER	uniprot:A0A0D9B2B6	ignore:TCDB::P21627	uniprot:A0A165KC95

livM	L-phenylalanine ABC transporter, permease component 2 (LivM)	curated:SwissProt::P22729	uniprot:A0A159ZYE0	ignore:TCDB::P21628	uniprot:A0A165KER0

livJ	L-phenylalanine ABC transporter, substrate-binding component LivJ/LivK	curated:CharProtDB::CH_107418	curated:TCDB::P0AD96	uniprot:A0A160A0J6	ignore:SwissProt::P21175	uniprot:A0A165KTD4

# Transporters were identified using
# query: transporter:phenylalanine:L-phenylalanine:phe
phenylalanine-transport: livF livG livH livM livJ

# RR42_RS33495 from Cupriavidus basilensis FW507-4G11 (A0A0C4YP23) is the phenylalanine transporter.
# Ignore A2RMP5, an ortholog from another Lactococcus.
aroP	L-phenylalanine:H+ symporter AroP	curated:TCDB::P15993	curated:TCDB::F2HN33	curated:TCDB::P24207	curated:TCDB::Q2VQZ4	curated:TCDB::Q46065	uniprot:A0A0C4YP23	ignore:SwissProt::A2RMP5

phenylalanine-transport: aroP

# non-specific eukaryotic transporters (i.e., Q01650) and the related serine/threonine exchanger SteT were excluded
# amino acid exporters such as yddG were excluded

# acetoacetate is an intermediate in tyrosine degradation
import leucine.steps:acetoacetate-degradation

# tyrosine is an intermediate in phenylalanine degradation
import tyrosine.steps:tyrosine-degradation

# phenylacetate is an intermediate in phenylalanine degradation
import phenylacetate.steps:phenylacetate-degradation phenylacetyl-CoA-degradation

# Several pathways involve transamination to phenylpyruvate
ARO8	L-phenylalanine transaminase	EC:	EC:	EC:	ignore:BRENDA::Q845W8	ignore:BRENDA::A0A060PQX5	ignore:SwissProt::P52878	ignore:BRENDA::O57946

ARO10	phenylpyruvate decarboxylase	EC:	ignore:BRENDA::A0A222AKA3

# The alpha subunit is MF179145 = A0A222AKA3 (which appears in BRENDA)
PPDCalpha	phenylpyruvate decarboxylase, alpha subunit	curated:BRENDA::A0A222AKA3
# The beta subunit is not curated but is MF179146 = ASO76824.1, identical in sequence to G1UHX5
PPDCbeta	phenylpyruvate decarboxylase, beta subunit	uniprot:G1UHX5

# Phenylpyruvate can be decarboxylated to phenylacetaldehyde by the typical
# homomeric enzyme, or by a heterodimer reported in Streptomyces virginiae
# (see PMID:28719183)
phenylpyruvate-decarboxylase: ARO10
phenylpyruvate-decarboxylase: PPDCalpha PPDCbeta

iorA	phenylpyruvate:ferredoxin oxidoreductase, IorA subunit	curated:BRENDA::O07835	curated:BRENDA::Q6LZB6	curated:BRENDA::Q6M0F5	curated:SwissProt::P80910

iorB	phenylpyruvate:ferredoxin oxidoreductase, IorB subunit	curated:BRENDA::O07836	curated:BRENDA::Q6LZB5	curated:BRENDA::Q6M0F6	curated:SwissProt::P80911

# A fused enzyme is described in Phaeobacter gallaeciensis (ior1 = A9ERV7 = I7EJ57, see PMC3346364).
iorAB	phenylpyruvate:ferredoxin oxidoreductase, fused IorA/IorB	curated:reanno::BFirm:BPHYT_RS02015	curated:reanno::Marino:GFF880	uniprot:I7EJ57

# 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-fd-oxidoreductase: iorA iorB
phenylpyruvate-fd-oxidoreductase: iorAB

# 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.
all: phenylalanine-transport ARO8 phenylpyruvate-fd-oxidoreductase phenylacetyl-CoA-degradation

pad-dh	phenylacetaldehyde dehydrogenase	EC:

# In the anaerobic pathway, the transaminase ARO8 forms
# phenylpyruvate, a carboxy-lyase forms phenylacetaldehyde,
# and a dehydrogenase (pad-dh) forms phenylacetate
all: phenylalanine-transport ARO8 phenylpyruvate-decarboxylase pad-dh phenylacetate-degradation

# This enzyme is ebA5005 = Q5P143. It runs in parallel with a
# phenylacetaldehyde dehydrogenase (PMID:24214948).
pfor	phenylacetaldeyde:ferredoxin oxidoreductase	EC:	uniprot:Q5P143

# Or, in a variation on the anaerobic pathway, the phenylacetaldehyde is oxidized to phenylacetate
# by phenylacetaldehyde:ferredoxin oxidoreductase (pfor).
all: phenylalanine-transport ARO8 phenylpyruvate-decarboxylase pfor phenylacetate-degradation

PAH	phenylalanine 4-monooxygenase	EC:

PCBD	pterin-4-alpha-carbinoalamine dehydratase	EC:

# In Pseudomonas, the cosubstrate of PAH is
# (6R)-L-threo-5,6,7,8-tetrahydroneopterin, also known as
# tetrahydromonapterin; in Chlorobaculum tepidum, it is
# (6R)-L-threo-5,6,7,8-tetrahydrobiopterin.
# EC: describes tetrahydrobiopterin reductases,
# while EC: describes bacterial dihydromonapterin reductases (folM in E. coli)
QDPR	6,7-dihydropteridine reductase	EC:	EC:	ignore:SwissProt::P26353	ignore:BRENDA::P15888	ignore:SwissProt::Q01234

# In the aerobic pathway, PAH forms tyrosine and hydroxylates its
# tetrahydropterin co-substrate; the tetrahydropterin is regenerated
# by dehydratase PCBD and reductase QDPR.
all: phenylalanine-transport PAH PCBD QDPR tyrosine-degradation



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About GapMind

Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.

A candidate for a step is "high confidence" if either:

where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").

Otherwise, a candidate is "medium confidence" if either:

Other blast hits with at least 50% coverage are "low confidence."

Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:

GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).

For more information, see:

If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know

by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory