Definition of L-tryptophan catabolism

GapMind for catabolism of small carbon sources

Definition of L-tryptophan catabolism

# Tryptophan degradation in GapMind is based on MetaCyc degradation pathways
# I via anthranilate (metacyc:TRPCAT-PWY),
# II via pyruvate (metacyc:TRYPDEG-PWY),
# or IX via 3-hydroxyanthranilate (metacyc:PWY-5655).
# Pathway XII (metacyc:PWY-6505) overlaps with pathway I and is also represented.
# The other MetaCyc pathways do not yield fixed carbon or are not reported in
# prokaryotes, and are not included.
# For example, pathway IV yields indole-3-lactate, which could potentially be oxidized to
# indole-3-acetate, which has a known catabolic pathway,
# but no prokaryotes are known to consume tryptophan
# this way.
# Pathway VIII yields tryptophol (also known as indole-3-ethanol),
# which could potentially be oxidized to indole-3-acetate and consumed.
# Pathways X and XIII yield indole-3-propionate, which may
# spontaneously oxidize to kynurate, but kynurate catabolism is not reported.

# Four-part transporter (bioMNY-type) with two ATPase (A1/A2) components, a transmembrane (T) component,
# and a substrate-specific (S) component.
# The A1A2T components are not specific to tryptophan.
trpP	energy-coupling factor transporter, tryptophan-specific (S) component TrpP	curated:SwissProt::O07515

# Orthologs may be annotated as ecfA1 or cbiO; these have the same function
# (but might not be part of a tryptophan transporting system).
ecfA1	energy-coupling factor transporter, ATPase 1 (A1) component	uniprot:P40735	ignore:TCDB::Q839D5	ignore:SwissProt::Q035B2	ignore:SwissProt::A2RI01	ignore:SwissProt::Q5M243	ignore:TCDB::Q03PY5	ignore:metacyc::G12WB-158-MONOMER	ignore:SwissProt::Q03ZL6	

# Orthologs may be annotated as ecfA2 or cbiO2; these have the same function
ecfA2	energy-coupling factor transporter, ATPase 2 (A2) component	uniprot:P70970	ignore:TCDB::Q839D4	ignore:SwissProt::Q5M244	ignore:SwissProt::A2RI02	ignore:SwissProt::Q035B3	ignore:TCDB::Q03PY6	ignore:metacyc::G12WB-159-MONOMER	ignore:SwissProt::Q03ZL5

# Ignore EcfT proteins from other bacteria
ecfT	energy-coupling factor transporter, transmembrane (T) component	curated:SwissProt::P70972	ignore:TCDB::I7BV49	ignore:SwissProt::Q5M245	ignore:SwissProt::A2RI03	ignore:SwissProt::Q035B4	ignore:metacyc::G12WB-160-MONOMER	ignore:TCDB::Q03PY7	ignore:SwissProt::Q03ZL4

# Transporters were identified using
# query: transporter:tryptophan:L-tryptophan:trp
tryptophan-transport: trpP ecfA1 ecfA2 ecfT

# AO353_05930 (A0A0N9WG97) from Pseudomonas fluorescens FW300-N2E3 is related to aroP and
#   is specifically improtant for tryptophan utilization (although more so if Trp is the nitrogen source).
# PfGW456L13_4291 (A0A293QSB2) from P. fluorescens GW4560-L13 is related to aroP and
#   is specifically important for tryptophan utilization.
#	Unfortunately A0A293QSB2 is no longer in UniProt; the closest remaining sequence is
#	Q4KIP0 (only 87% identical).
# FywP (A2RMP5) may well be a tryptophan transporter as well, so ignore.
aroP	tryptophan:H+ symporter AroP	curated:TCDB::P15993	curated:TCDB::F2HN33	curated:TCDB::Q2VQZ4	curated:TCDB::Q46065	uniprot:A0A0N9WG97	uniprot:Q4KIP0	ignore:SwissProt::A2RMP5	ignore:reanno::pseudo5_N2C3_1:AO356_18530
tryptophan-transport: aroP

tnaB	tryptophan:H+ symporter TnaB	curated:CharProtDB::CH_000783	curated:SwissProt::Q02DS7	curated:TCDB::P0AAD2
tryptophan-transport: tnaB

TAT	tryptophan permease	curated:CharProtDB::CH_091156	curated:CharProtDB::CH_091631
tryptophan-transport: TAT

tnaT	tryptophan:Na+ symporter TnaT	curated:TCDB::O50649
tryptophan-transport: tnaT

# Serine/threonine exchangers and non-specific eukaryotic amino acid transporters were ignored

# Tryptophan catabolism often involves anthranilate (2-aminobenzoate),
# 3-hydroxyanthranilate, or catechol (1,2-dihydroxybenzene) as
# intermediates

# acetaldehyde is also an intermediate
import ethanol.steps:acetaldehyde-degradation

# 2-hydroxypenta-2,4-dienoate-degradation (HPD), 2-hydroxymuconate 6-semialdehyde,
# and 3-oxoadipate are intermediates in catechol degradation.
# pcaD is 3-oxoadipate enol-lactone hydrolase
import 4-hydroxybenzoate.steps:2-hydroxypenta-2,4-dienoate-degradation 2-hydroxymuconate-6-semialdehyde-degradation 3-oxoadipate-degradation pcaD

# Catechol degradation

# BRENDA misannotates P23103 as the P. putida xylE (that should be, P06622)
xylE	catechol 2,3-dioxygenase	EC:1.13.11.2	ignore:BRENDA::P23103

# In MetaCyc pathway catechol degradation to HPD I (meta-cleavage, metacyc:P183-PWY),
# dioxygenase xylE converts catechol to
# (2Z,4E)-2-hydroxy-6-oxohexa-2,4-dienoate (also known as
# 2-hydroxymuconate 6-semialdehyde).
# (Catechol degradation to HPD II also involves xylE and HPD, metacyc:PWY-5419.) 
catechol-degradation: xylE 2-hydroxymuconate-6-semialdehyde-degradation

# Ignore two protein fragments for catA
catA	catechol 1,2-dioxygenase	EC:1.13.11.1	ignore:CharProtDB::CH_012040	ignore:SwissProt::P83715
catB	muconate cycloisomerase	EC:5.5.1.1
catC	muconolactone isomerase	EC:5.3.3.4

# In MetaCyc pathway catechol degradation III (ortho-cleavage, metacyc:PWY-5417),
# the 1,2-dioxygenase catA forms cis,cis-muconate, a cycloisomerase forms
# (+)-muconolactone, an isomerase converts this to
# (4,5-dihydro-5-oxofuran-2-yl)-acetate (also known as 3-oxoadipate
# enol lactone), and a hydrolase cleaves this to 3-oxoadipate.
catechol-degradation: catA catB catC pcaD 3-oxoadipate-degradation

# 3-hydroxyanthranilate (2-amino-3-hydroxybenzoate) is an intermediate
# in anthranilate or tryptophan degradation

nbaC	3-hydroxyanthranilate 3,4-dioxygenase	EC:1.13.11.6
nbaD	2-amino-3-carboxymuconate-6-semialdehyde decarboxylase	EC:4.1.1.45
nbaE	2-aminomuconate 6-semialdehyde dehydrogenase	EC:1.2.1.32
nbaF	2-aminomuconate deaminase	EC:3.5.99.5
nbaG	2-oxo-3-hexenedioate decarboxylase	EC:4.1.1.77

# 3-hydroxyanthranilate degradation is part of
# L-tryptophan degradation pathway XII (metacyc:PWY-6505).
# Dioxygenase NbaC cleaves the aromatic ring,  yielding 2-amino-3-carboxymuconate
# 6-semialdehyde, a decarboxylase forms (2Z,4E)-2-aminomuconate
# semialdehyde, a dehydrogenase forms (2Z,4E)-2-aminomuconate, a
# deaminase forms (3E)-2-oxo-3-hexenedioate (also known as
# 2-oxalocrotonate), and a decarboxylase forms
# (2Z)-2-hydroxypenta-2,4-dienoate (HPD).
3-hydroxyanthranilate-degradation: nbaC nbaD nbaE nbaF nbaG 2-hydroxypenta-2,4-dienoate-degradation

antA	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), large subunit AntA	curated:SwissProt::O85673	curated:reanno::WCS417:GFF4629	curated:reanno::pseudo13_GW456_L13:PfGW456L13_2740	curated:reanno::pseudo3_N2E3:AO353_05950	ignore_other:1.14.12.1

antB	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), small subunit AntB	curated:SwissProt::O85674	curated:reanno::WCS417:GFF4630	curated:reanno::pseudo13_GW456_L13:PfGW456L13_2739	curated:reanno::pseudo3_N2E3:AO353_05955	ignore_other:1.14.12.1

antC	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), electron transfer component AntC	curated:SwissProt::O85675	curated:reanno::WCS417:GFF4631	curated:reanno::pseudo13_GW456_L13:PfGW456L13_2738	ignore_other:1.14.12.1

# There are two forms of anthranilate dioxygenase, 3-subunit antABC or 4-subunit andAabcd.
anthranilate-dioxygenase: antA antB antC

andAa	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), ferredoxin--NAD(+) reductase component AndAa	curated:SwissProt::Q84BZ0	ignore_other:1.14.12.1

andAb	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), ferredoxin subunit AndAb	curated:SwissProt::Q84BZ1	ignore_other:1.14.12.1

andAc	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), large subunit AndAc	curated:SwissProt::Q84BZ3	ignore_other:1.14.12.1

andAd	athranilate 1,2-dioxygenase (deaminating, decarboxylating), small subunit AndAd	curated:SwissProt::Q84BZ2	ignore_other:1.14.12.1

anthranilate-dioxygenase: andAa andAb andAc andAd

# In MetaCyc pathway anthranilate degradation I (metacyc:PWY-6079),
# a dioxygenase cleaves off carbon dioxide and ammonia, leaving catechol.
anthranilate-degradation: anthranilate-dioxygenase catechol-degradation

hpaH	anthranilate 3-monooxygenase (hydroxylase), FADH2-dependent	EC:1.14.14.8

# In MetaCyc pathway anthranilate degradation IV (metacyc:PWY-6504),
# anthranilate hydroxylase/monooxygenase (hpaH) yields
# 3-hydroxyanthranilate.
#
# Additional pathways are not included: the fate of
# 2-amino-5-oxocyclohex-1-enecarboxyl-CoA is not known
# (metacyc:PWY-6077), and anthraniloyl-CoA reductase
# (the only anaerobic route known, metacyc:2AMINOBENZDEG-PWY) has not
# been linked to sequence.
anthranilate-degradation: hpaH 3-hydroxyanthranilate-degradation

kynA	tryptophan 2,3-dioxygenase	EC:1.13.11.11	EC:1.13.11.52
# MONOMER-19595 is involved in echinomycin biosynthesis and its molecular function
# is controversial, see the MetaCyc entry.
kynB	kynurenine formamidase	EC:3.5.1.9	ignore:metacyc::MONOMER-19595

# 3-hydroxykynurenine hydrolase and kynurenine hydrolase
# are described by the same EC number.
kyn	kynureninase	EC:3.7.1.3

# In pathway I, dioxygenase kynA opens the non-aromatic ring, to N-formyl-L-kynureine,
# a hydrolase yields L-kynurenine (and formate),
# and a hydrolase yields anthranilate and L-alanine.
all: tryptophan-transport kynA kynB kyn anthranilate-degradation

# MONOMER-7584 and -7541 carry out the same reaction but were not linked to the EC number
tnaA	tryptophanase	EC:4.1.99.1	curated:metacyc::MONOMER-7584	curated:metacyc::MONOMER-7541

# In pathway II, the tryptophan is hydrolyzed to indole and pyruvate,
# and the indole may be secreted (as in E. coli).
all: tryptophan-transport tnaA

sibC	L-kynurenine 3-monooxygenase	EC:1.14.13.9

# In pathway IX, dioxygenase kynA forms N-formyl-L-kynurenine and a hydrolase
# forms L-kynurenine, as in pathway I; then, oxygenase sibC forms
# 3-hydroxy-L-kynurenine, which is hydrolyzed to L-alanine and
# 3-hydroxyanthranilate.
all: tryptophan-transport kynA kynB sibC kyn 3-hydroxyanthranilate-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:

ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.

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:

ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
HMMer finds a hit (regardless of coverage or other bits).

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:

our ignorance of proteins' functions,
omissions in the gene models,
frame-shift errors in the genome sequence, or
the organism lacks the pathway.

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:

the paper from 2019 on GapMind for amino acid biosynthesis
the paper from 2022 on GapMind for carbon sources
the source code
instructions for running GapMind on your computer

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

GapMind for catabolism of small carbon sources