As text, or see rules and steps
# 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
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:
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