L-tryptophan catabolism in Cupriavidus basilensis 4G11

GapMind for catabolism of small carbon sources

L-tryptophan catabolism in Cupriavidus basilensis 4G11

Best path

aroP, kynA, kynB, kyn, antA, antB, antC, xylE, praB, praC, praD, mhpD, mhpE, adh, ackA, pta

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:

antA, antB and antC
or andAa, andAb, andAc and andAd
Comment: There are two forms of anthranilate dioxygenase, 3-subunit antABC or 4-subunit andAabcd.

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:

trpP, ecfA1, ecfA2 and ecfT
or aroP
or tnaB
or TAT
or tnaT
Comment: Transporters were identified using query: transporter:tryptophan:L-tryptophan:trp

47 steps (39 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
aroP	tryptophan:H+ symporter AroP	RR42_RS33495	RR42_RS05070
kynA	tryptophan 2,3-dioxygenase	RR42_RS15390
kynB	kynurenine formamidase	RR42_RS15380	RR42_RS16840
kyn	kynureninase	RR42_RS15385
antA	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), large subunit AntA	RR42_RS23500
antB	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), small subunit AntB	RR42_RS23495
antC	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), electron transfer component AntC	RR42_RS23490	RR42_RS32665
xylE	catechol 2,3-dioxygenase	RR42_RS32655	RR42_RS34600
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	RR42_RS05110	RR42_RS32650
praC	2-hydroxymuconate tautomerase	RR42_RS32635	RR42_RS15120
praD	2-oxohex-3-enedioate decarboxylase	RR42_RS32640	RR42_RS32645
mhpD	2-hydroxypentadienoate hydratase	RR42_RS27885	RR42_RS32645
mhpE	4-hydroxy-2-oxovalerate aldolase	RR42_RS27900	RR42_RS32625
adh	acetaldehyde dehydrogenase (not acylating)	RR42_RS34255	RR42_RS25005
ackA	acetate kinase	RR42_RS03800	RR42_RS22745
pta	phosphate acetyltransferase	RR42_RS33690	RR42_RS03805
Alternative steps:
acs	acetyl-CoA synthetase, AMP-forming	RR42_RS13880	RR42_RS10650
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	RR42_RS27895	RR42_RS32630
andAa	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), ferredoxin--NAD(+) reductase component AndAa	RR42_RS26430	RR42_RS29850
andAb	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), ferredoxin subunit AndAb	RR42_RS26435	RR42_RS33940
andAc	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), large subunit AndAc	RR42_RS26425	RR42_RS33930
andAd	athranilate 1,2-dioxygenase (deaminating, decarboxylating), small subunit AndAd	RR42_RS33935	RR42_RS26420
catA	catechol 1,2-dioxygenase	RR42_RS23505	RR42_RS32880
catB	muconate cycloisomerase	RR42_RS21835
catC	muconolactone isomerase	RR42_RS21840	RR42_RS10025
catI	3-oxoadipate CoA-transferase subunit A (CatI)
catJ	3-oxoadipate CoA-transferase subunit B (CatJ)	RR42_RS31950
ecfA1	energy-coupling factor transporter, ATPase 1 (A1) component	RR42_RS27115	RR42_RS09480
ecfA2	energy-coupling factor transporter, ATPase 2 (A2) component	RR42_RS16445	RR42_RS30240
ecfT	energy-coupling factor transporter, transmembrane (T) component
hpaH	anthranilate 3-monooxygenase (hydroxylase), FADH2-dependent
nbaC	3-hydroxyanthranilate 3,4-dioxygenase	RR42_RS05080
nbaD	2-amino-3-carboxymuconate-6-semialdehyde decarboxylase	RR42_RS05075
nbaE	2-aminomuconate 6-semialdehyde dehydrogenase	RR42_RS05110	RR42_RS32650
nbaF	2-aminomuconate deaminase	RR42_RS05085	RR42_RS07975
nbaG	2-oxo-3-hexenedioate decarboxylase	RR42_RS32640	RR42_RS32645
pcaD	3-oxoadipate enol-lactone hydrolase	RR42_RS21850	RR42_RS32050
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	RR42_RS35915	RR42_RS26090
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)	RR42_RS35925	RR42_RS10005
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)	RR42_RS35920	RR42_RS10010
sibC	L-kynurenine 3-monooxygenase
TAT	tryptophan permease	RR42_RS11100	RR42_RS05070
tnaA	tryptophanase
tnaB	tryptophan:H+ symporter TnaB
tnaT	tryptophan:Na+ symporter TnaT
trpP	energy-coupling factor transporter, tryptophan-specific (S) component TrpP
xylF	2-hydroxymuconate semialdehyde hydrolase	RR42_RS27870	RR42_RS31825

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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Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
SQLite3 databases

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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