L-lysine catabolism in Burkholderia phytofirmans PsJN

GapMind for catabolism of small carbon sources

L-lysine catabolism in Burkholderia phytofirmans PsJN

Best path

argT, hisM, hisQ, hisP, cadA, patA, patD, davT, davD, gcdG, gcdH, ech, fadB, atoB

Also see fitness data for the top candidates

Rules

Overview: Lysine degradation in GapMind is based on many metacyc pathways (link), including L-lysine degradation I via cadaverine (link), pathway IV via lysine monooxygenase (link), pathway V via D-lysine (link), pathway VI via lysine 6-aminotransferase (link), pathway VIII via lysine 6-dehydrogenase (link), and fermentation to acetate and butanoate (link). Pathway X (link) is similar to pathway I (with cadaverine and glutarate as intermediates), but glutarate is consumed via glutaryl-CoA (as in pathway IV); it does not introduce any new steps. Pathways II (L-pipecolate pathway) and III (via N6-acetyllysine) and VII (via 6-amino-2-oxohexanoate) and IX (similar to pathway IV) and XI (via saccharopine) are not thought to occur in prokaryotes and are not included in GapMind.

all:

lysine-transport, cadA, patA, patD and 5-aminovalerate-degradation
or lysine-transport, davB, davA and 5-aminovalerate-degradation
or lysine-transport, alr, amaD, dpkA, amaA, amaB and L-2-aminoadipate-degradation
or lysine-transport, lat, amaB and L-2-aminoadipate-degradation
or lysine-transport, lysDH, amaB and L-2-aminoadipate-degradation
or lysine-transport, kamA, kamD, kamE, kdd, kce, kal, bcd, etfA, etfB, ctfA, ctfB and atoB
Comment: In pathway I, lysine is decarboxylated by cadA to cadaverine (1,5-diaminopentane), transaminated to 5-aminopentanal by patA, and oxidized to 5-aminovalerate by patD. In pathway IV, the monooxygenase/decarboxylase davB forms 5-aminopentanamide, which is hydrolyzed to 5-aminovalerate (5-aminopentanoate). In pathway V, the racemase alr forms D-lysine, which is oxidized to 6-amino-2-oxo-hexanoate, spontaneously decarboxylates to 1-piperideine-2-carboxylate, a reductase forms L-pipecolate, an oxidase forms 1-piperideine-6-carboxylate, and a dehydrogenase forms L-2-aminoadipate. In pathway VI, lysine 6-aminotransferase (lat) forms (S)-2-amino-6-oxohexanoate, which spontaenously dehydrates to 1-piperideine 6-carboxylate, and a dehydrogenase forms L-2-aminoadipate In pathway VIII, L-lysine 6-dehydrogenase (lysDH) forms (S)-2-amino-6-oxohexanoate, which spontaenously dehydrates to 1-piperideine 6-carboxylate, and a dehydrogenase forms L-2-aminoadipate. In the fermentative pathway, lysine 2,3-aminomutase (kamA) forms L-beta-lysine, another aminomutase forms (3S,5S)-3,5-diaminohexanoate, a dehydrogenase (deaminating) forms (S)-5-amino-3-oxohexanoate, a cleavage enzyme (thiolase) uses acetyl-CoA to form (S)-3-aminobutanoyl-CoA and acetoacetate, a deaminase forms crotonyl-CoA, a dehydrogenase forms butanoyl-CoA, a CoA-transferase converts the butanoyl-CoA and acetoacetate to butanoate (a waste product) and acetoacetyl-CoA, and a C-acetyltransferase (atoB) splits acetyl-CoA to two acetyl-CoA.

L-2-aminoadipate-degradation: lysN, hglS and ydiJ

Comment: L-2-aminoadipate is an intermediate in L-lysine degradation pathways V and VI (link, link). A transaminase forms 2-oxoadipate, a oxygenase/decarboxylase (D-2-hydroxyglutarate synthase) forms (R)-2-hydroxyglutarate, and a dehydrogenase forms 2-oxoglutarate, which is an intermediate in the TCA cycle.

5-aminovalerate-degradation: davT, davD and glutarate-degradation

Comment: 5-aminovalerate is an intermediate in L-lysine degradation (link, link). It is transaminated to glutarate semialdehyde and oxidized to glutarate. (A fermentative pathway via 5-hydroxyvalerate has also been reported, but does not seem to be fully linked to sequence; see pathway 5 of PMID:11759672.)

glutarate-degradation:

glaH and lhgD
or gcdG and glutaryl-CoA-degradation
Comment: Glutarate is an intermediate in L-lysine degradation. As part of MetaCyc pathway L-lysine degradation I (link), gluratate is hydroxylated to L-2-hydroxyglutarate (also known as (S)-2-hydroxyglutarate) by a 2-oxoglutarate-dependent oxidase. This reaction releases succinate (a TCA cycle intermediate) and CO2. A dehydrogenase then oxidizes to L-2-hydroxyglutarate to regenerate 2-oxoglutarate. Alternatively, as part of pathway IV (link), glutarate can be activated to glutaryl-CoA by a CoA-transferase. Glutaryl-CoA degradation (link) involves glutaryl-CoA dehydrogenase (decarboxylating) to crotonyl-CoA (trans-but-2-enoyl-CoA), hydration to (S)-hydroxybutanoyl-CoA, oxidization to acetoacetyl-CoA, and cleavage by a C-acetyltransferase to two acetyl-CoA.

glutaryl-CoA-degradation: gcdH, ech, fadB and atoB

Comment: In MetaCyc pathway glutaryl-CoA degradation (link), glutaryl-CoA is oxidized to (E)-glutaconyl-CoA and oxidatively decarboxylated to crotonyl-CoA (both by the same enzyme), hydrated to 3-hydroxybutanoyl-CoA, oxidized to acetoacetyl-CoA, and cleaved to two acetyl-CoA.

lysine-transport:

lysP
or LHT
or Slc7a1
or lysL
or argT, hisM, hisQ and hisP
or bgtB and hisP
Comment: Transporters were identified using query: transporter:lysine:L-lysine:lys:L-lys

44 steps (34 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
argT	L-lysine ABC transporter, substrate-binding component ArgT	BPHYT_RS35100	BPHYT_RS29525
hisM	L-lysine ABC transporter, permease component 1 (HisM)	BPHYT_RS05500	BPHYT_RS07680
hisQ	L-lysine ABC transporter, permease component 2 (HisQ)	BPHYT_RS05505	BPHYT_RS07675
hisP	L-lysine ABC transporter, ATPase component HisP	BPHYT_RS24015	BPHYT_RS07685
cadA	lysine decarboxylase	BPHYT_RS04980	BPHYT_RS06500
patA	cadaverine aminotransferase	BPHYT_RS27170	BPHYT_RS07695
patD	5-aminopentanal dehydrogenase	BPHYT_RS09900	BPHYT_RS25160
davT	5-aminovalerate aminotransferase	BPHYT_RS22435	BPHYT_RS07695
davD	glutarate semialdehyde dehydrogenase	BPHYT_RS22430	BPHYT_RS34305
gcdG	succinyl-CoA:glutarate CoA-transferase	BPHYT_RS13985	BPHYT_RS31850
gcdH	glutaryl-CoA dehydrogenase	BPHYT_RS03780	BPHYT_RS23260
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BPHYT_RS17335	BPHYT_RS28020
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	BPHYT_RS13545	BPHYT_RS03225
atoB	acetyl-CoA C-acetyltransferase	BPHYT_RS09150	BPHYT_RS09180
Alternative steps:
alr	lysine racemase	BPHYT_RS12240
amaA	L-pipecolate oxidase	BPHYT_RS13575	BPHYT_RS30200
amaB	L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd)	BPHYT_RS32650	BPHYT_RS28770
amaD	D-lysine oxidase	BPHYT_RS10270	BPHYT_RS22250
bcd	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit	BPHYT_RS28040	BPHYT_RS02220
bgtB	L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)
ctfA	butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit	BPHYT_RS13675	BPHYT_RS21415
ctfB	butanoyl-CoA:acetoacetate CoA-transferase, beta subunit	BPHYT_RS13670	BPHYT_RS21420
davA	5-aminovaleramidase	BPHYT_RS22155	BPHYT_RS00250
davB	L-lysine 2-monooxygenase
dpkA	1-piperideine-2-carboxylate reductase	BPHYT_RS24365	BPHYT_RS21000
etfA	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit	BPHYT_RS14800	BPHYT_RS20830
etfB	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit	BPHYT_RS20825	BPHYT_RS14805
glaH	glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)
hglS	D-2-hydroxyglutarate synthase
kal	3-aminobutyryl-CoA deaminase
kamA	L-lysine 2,3-aminomutase
kamD	L-beta-lysine 5,6-aminomutase, alpha subunit
kamE	L-beta-lysine 5,6-aminomutase, beta subunit
kce	(S)-5-amino-3-oxohexanoate cleavage enzyme	BPHYT_RS31475	BPHYT_RS22385
kdd	3,5-diaminohexanoate dehydrogenase
lat	L-lysine 6-aminotransferase	BPHYT_RS22435	BPHYT_RS10155
lhgD	L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)	BPHYT_RS28480	BPHYT_RS01855
LHT	L-lysine transporter
lysDH	L-lysine 6-dehydrogenase	BPHYT_RS11250
lysL	L-lysine transporter LysL	BPHYT_RS27675
lysN	2-aminoadipate transaminase	BPHYT_RS05965	BPHYT_RS22435
lysP	L-lysine:H+ symporter LysP	BPHYT_RS15500	BPHYT_RS21680
Slc7a1	L-lysine transporter Slc7a1	BPHYT_RS33230	BPHYT_RS01785
ydiJ	(R)-2-hydroxyglutarate dehydrogenase	BPHYT_RS32905	BPHYT_RS13750

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.

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