L-tryptophan catabolism in Sphingomonas laterariae LNB2

GapMind for catabolism of small carbon sources

L-tryptophan catabolism in Sphingomonas laterariae LNB2

Best path

aroP, kynA, kynB, kyn, hpaH, nbaC, nbaD, nbaE, nbaF, nbaG, mhpD, mhpE, ald-dh-CoA

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 (29 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
aroP	tryptophan:H+ symporter AroP	CHB74_RS04175
kynA	tryptophan 2,3-dioxygenase	CHB74_RS10760
kynB	kynurenine formamidase	CHB74_RS13165
kyn	kynureninase	CHB74_RS04260
hpaH	anthranilate 3-monooxygenase (hydroxylase), FADH2-dependent
nbaC	3-hydroxyanthranilate 3,4-dioxygenase	CHB74_RS04290
nbaD	2-amino-3-carboxymuconate-6-semialdehyde decarboxylase	CHB74_RS04295
nbaE	2-aminomuconate 6-semialdehyde dehydrogenase	CHB74_RS04270	CHB74_RS12680
nbaF	2-aminomuconate deaminase	CHB74_RS04285	CHB74_RS20445
nbaG	2-oxo-3-hexenedioate decarboxylase	CHB74_RS04280	CHB74_RS01225
mhpD	2-hydroxypentadienoate hydratase	CHB74_RS04275	CHB74_RS01225
mhpE	4-hydroxy-2-oxovalerate aldolase	CHB74_RS01215	CHB74_RS13740
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	CHB74_RS01220
Alternative steps:
ackA	acetate kinase	CHB74_RS18125	CHB74_RS20060
acs	acetyl-CoA synthetase, AMP-forming	CHB74_RS04770	CHB74_RS05000
adh	acetaldehyde dehydrogenase (not acylating)	CHB74_RS04745	CHB74_RS12680
andAa	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), ferredoxin--NAD(+) reductase component AndAa	CHB74_RS01685	CHB74_RS13440
andAb	anthranilate 1,2-dioxygenase (deaminating, decarboxylating), ferredoxin subunit AndAb
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
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)	CHB74_RS04920
ecfA1	energy-coupling factor transporter, ATPase 1 (A1) component	CHB74_RS12660	CHB74_RS12605
ecfA2	energy-coupling factor transporter, ATPase 2 (A2) component	CHB74_RS02270	CHB74_RS00790
ecfT	energy-coupling factor transporter, transmembrane (T) component
pcaD	3-oxoadipate enol-lactone hydrolase	CHB74_RS05545
pcaF	succinyl-CoA:acetyl-CoA C-succinyltransferase	CHB74_RS13115	CHB74_RS18155
pcaI	3-oxoadipate CoA-transferase subunit A (PcaI)	CHB74_RS04050
pcaJ	3-oxoadipate CoA-transferase subunit B (PcaJ)	CHB74_RS04045
praB	2-hydroxymuconate 6-semialdehyde dehydrogenase	CHB74_RS04270	CHB74_RS12680
praC	2-hydroxymuconate tautomerase
praD	2-oxohex-3-enedioate decarboxylase	CHB74_RS04280	CHB74_RS01225
pta	phosphate acetyltransferase	CHB74_RS18130	CHB74_RS20065
sibC	L-kynurenine 3-monooxygenase
TAT	tryptophan permease	CHB74_RS04175
tnaA	tryptophanase
tnaB	tryptophan:H+ symporter TnaB
tnaT	tryptophan:Na+ symporter TnaT
trpP	energy-coupling factor transporter, tryptophan-specific (S) component TrpP
xylE	catechol 2,3-dioxygenase	CHB74_RS17930	CHB74_RS02615
xylF	2-hydroxymuconate semialdehyde hydrolase	CHB74_RS13705	CHB74_RS17755

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 24 2021. The underlying query database was built on Sep 17 2021.

Downloads

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

Related tools

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