L-tryptophan catabolism in Escherichia coli BW25113
Best path
aroP, tnaA
Also see fitness data for the top candidates
Rules
Overview: Tryptophan degradation in GapMind is based on MetaCyc degradation pathways I via anthranilate (link), II via pyruvate (link), or IX via 3-hydroxyanthranilate (link). Pathway XII (link) 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.
- all:
- tryptophan-transport, kynA, kynB, kyn and anthranilate-degradation
- or tryptophan-transport and tnaA
- or tryptophan-transport, kynA, kynB, sibC, kyn and 3-hydroxyanthranilate-degradation
- Comment: 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. In pathway II, the tryptophan is hydrolyzed to indole and pyruvate, and the indole may be secreted (as in E. coli). 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.
- anthranilate-degradation:
- anthranilate-dioxygenase and catechol-degradation
- or hpaH and 3-hydroxyanthranilate-degradation
- Comment: In MetaCyc pathway anthranilate degradation I (link), a dioxygenase cleaves off carbon dioxide and ammonia, leaving catechol. In MetaCyc pathway anthranilate degradation IV (link), 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 (link), and anthraniloyl-CoA reductase (the only anaerobic route known, link) has not been linked to sequence.
- anthranilate-dioxygenase:
- 3-hydroxyanthranilate-degradation: nbaC, nbaD, nbaE, nbaF, nbaG and 2-hydroxypenta-2,4-dienoate-degradation
- Comment: 3-hydroxyanthranilate degradation is part of L-tryptophan degradation pathway XII (link). 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).
- catechol-degradation:
- xylE and 2-hydroxymuconate-6-semialdehyde-degradation
- or catA, catB, catC, pcaD and 3-oxoadipate-degradation
- Comment: In MetaCyc pathway catechol degradation to HPD I (meta-cleavage, link), 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, link.) In MetaCyc pathway catechol degradation III (ortho-cleavage, link), 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.
- 3-oxoadipate-degradation: 3-oxodipate-CoA-transferase and pcaF
- Comment: MetaCyc pathway 3-oxoadipate degradation (link) involves activation by CoA (using succinyl-CoA) and a thiolase (succinyltransferase) reaction that splits it to acetyl-CoA and succinyl-CoA.
- 2-hydroxymuconate-6-semialdehyde-degradation:
- praB, praC, praD and 2-hydroxypenta-2,4-dienoate-degradation
- or xylF and 2-hydroxypenta-2,4-dienoate-degradation
- Comment: Dehydrogenase praB forms 2-hydroxymuconate, tautomerase praC forms (3E)-2-oxohex-3-enedioate (2-oxalocrotonate), and decarboxylase praD yields 2-hydroxypenta-2,4-dienoate (HPD). (This series of steps is part of protocatechuate para-cleavage, link, or catechol degradation II, link.) Or, hydrolase xylF forms HPD and formate. (This is part of a MetaCyc pathway for catechol degradation, link.)
- 2-hydroxypenta-2,4-dienoate-degradation: mhpD, mhpE and acetaldehyde-degradation
- Comment: (2Z)-2-hydroxypenta-2,4-dienoate (HPD) is a common intermediate in the aerobic degradation of many aromatic compounds. In MetaCyc pathway 2-hydroxypenta-2,4-dienoate degradation (link), HPD is hydrated to (S)-4-hydroxy-2-oxopentanoate and an aldolase cleaves it to pyruvate and acetaldehyde.
- 3-oxodipate-CoA-transferase:
- pcaI and pcaJ
- or catI and catJ
- Comment: Two different types of 3-oxoadipate CoA-transferases (EC 2.8.3.6) are known. They are both heteromeric with each subunit containing a CoA-transferase domain
- acetaldehyde-degradation:
- ald-dh-CoA
- or adh and acs
- or adh, ackA and pta
- Comment: Acetaldehyde can be oxidized to acetyl-CoA, or oxidized to acetate and activated to acetyl-CoA by either acetyl-CoA synthetase (acs) or by acetate kinase (ackA) and phosphate acetyltransferase (pta).
- tryptophan-transport:
47 steps (24 with candidates)
Or see definitions of steps
| Step | Description | Best candidate | 2nd candidate |
|---|
| aroP | tryptophan:H+ symporter AroP | b0112 | b0576 |
| tnaA | tryptophanase | b3708 | |
| Alternative steps: |
| ackA | acetate kinase | b3115 | b2296 |
| acs | acetyl-CoA synthetase, AMP-forming | b4069 | b0335 |
| adh | acetaldehyde dehydrogenase (not acylating) | b1746 | b1241 |
| ald-dh-CoA | acetaldehyde dehydrogenase, acylating | b1241 | b2455 |
| andAa | anthranilate 1,2-dioxygenase (deaminating, decarboxylating), ferredoxin--NAD(+) reductase component AndAa | b2542 | b2711 |
| andAb | anthranilate 1,2-dioxygenase (deaminating, decarboxylating), ferredoxin subunit AndAb | b2540 | |
| andAc | anthranilate 1,2-dioxygenase (deaminating, decarboxylating), large subunit AndAc | | |
| andAd | athranilate 1,2-dioxygenase (deaminating, decarboxylating), small subunit AndAd | | |
| antA | anthranilate 1,2-dioxygenase (deaminating, decarboxylating), large subunit AntA | b1802 | |
| antB | anthranilate 1,2-dioxygenase (deaminating, decarboxylating), small subunit AntB | | |
| antC | anthranilate 1,2-dioxygenase (deaminating, decarboxylating), electron transfer component AntC | | |
| catA | catechol 1,2-dioxygenase | | |
| catB | muconate cycloisomerase | | |
| catC | muconolactone isomerase | | |
| catI | 3-oxoadipate CoA-transferase subunit A (CatI) | | |
| catJ | 3-oxoadipate CoA-transferase subunit B (CatJ) | | |
| ecfA1 | energy-coupling factor transporter, ATPase 1 (A1) component | b2677 | b0855 |
| ecfA2 | energy-coupling factor transporter, ATPase 2 (A2) component | b1917 | b0809 |
| ecfT | energy-coupling factor transporter, transmembrane (T) component | | |
| hpaH | anthranilate 3-monooxygenase (hydroxylase), FADH2-dependent | | |
| kyn | kynureninase | | |
| kynA | tryptophan 2,3-dioxygenase | | |
| kynB | kynurenine formamidase | | |
| mhpD | 2-hydroxypentadienoate hydratase | b0350 | |
| mhpE | 4-hydroxy-2-oxovalerate aldolase | b0352 | b2245 |
| nbaC | 3-hydroxyanthranilate 3,4-dioxygenase | | |
| nbaD | 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase | | |
| nbaE | 2-aminomuconate 6-semialdehyde dehydrogenase | b0312 | b1300 |
| nbaF | 2-aminomuconate deaminase | | |
| nbaG | 2-oxo-3-hexenedioate decarboxylase | b0350 | |
| pcaD | 3-oxoadipate enol-lactone hydrolase | | |
| pcaF | succinyl-CoA:acetyl-CoA C-succinyltransferase | b1397 | b2224 |
| pcaI | 3-oxoadipate CoA-transferase subunit A (PcaI) | b2221 | |
| pcaJ | 3-oxoadipate CoA-transferase subunit B (PcaJ) | b2222 | |
| praB | 2-hydroxymuconate 6-semialdehyde dehydrogenase | b0312 | b1300 |
| praC | 2-hydroxymuconate tautomerase | | |
| praD | 2-oxohex-3-enedioate decarboxylase | b0350 | |
| pta | phosphate acetyltransferase | b2297 | b2458 |
| sibC | L-kynurenine 3-monooxygenase | | |
| TAT | tryptophan permease | b2156 | b0112 |
| tnaB | tryptophan:H+ symporter TnaB | b3709 | b3161 |
| tnaT | tryptophan:Na+ symporter TnaT | | |
| trpP | energy-coupling factor transporter, tryptophan-specific (S) component TrpP | | |
| xylE | catechol 2,3-dioxygenase | | |
| xylF | 2-hydroxymuconate semialdehyde hydrolase | b0349 | |
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 17 2021. The underlying query database was built on Sep 17 2021.
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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:
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