L-lysine catabolism in Azospirillum brasilense Sp245

GapMind for catabolism of small carbon sources

L-lysine catabolism in Azospirillum brasilense Sp245

Best path

argT, hisM, hisQ, hisP, davB, davA, 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 (31 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
argT	L-lysine ABC transporter, substrate-binding component ArgT	AZOBR_RS27130	AZOBR_RS00685
hisM	L-lysine ABC transporter, permease component 1 (HisM)	AZOBR_RS00675	AZOBR_RS23520
hisQ	L-lysine ABC transporter, permease component 2 (HisQ)	AZOBR_RS00680	AZOBR_RS23520
hisP	L-lysine ABC transporter, ATPase component HisP	AZOBR_RS00690	AZOBR_RS08670
davB	L-lysine 2-monooxygenase
davA	5-aminovaleramidase	AZOBR_RS30770	AZOBR_RS08170
davT	5-aminovalerate aminotransferase	AZOBR_RS19630	AZOBR_RS19025
davD	glutarate semialdehyde dehydrogenase	AZOBR_RS09720	AZOBR_RS19635
gcdG	succinyl-CoA:glutarate CoA-transferase	AZOBR_RS19675	AZOBR_RS29180
gcdH	glutaryl-CoA dehydrogenase	AZOBR_RS19670	AZOBR_RS22310
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	AZOBR_RS01260	AZOBR_RS26485
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	AZOBR_RS20225	AZOBR_RS29225
atoB	acetyl-CoA C-acetyltransferase	AZOBR_RS30610	AZOBR_RS28180
Alternative steps:
alr	lysine racemase	AZOBR_RS07795	AZOBR_RS08350
amaA	L-pipecolate oxidase	AZOBR_RS32385	AZOBR_RS25655
amaB	L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd)	AZOBR_RS32620	AZOBR_RS29185
amaD	D-lysine oxidase	AZOBR_RS30970
bcd	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit	AZOBR_RS22300	AZOBR_RS22365
bgtB	L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)
cadA	lysine decarboxylase	AZOBR_RS14105	AZOBR_RS10990
ctfA	butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit
ctfB	butanoyl-CoA:acetoacetate CoA-transferase, beta subunit
dpkA	1-piperideine-2-carboxylate reductase	AZOBR_RS31690	AZOBR_RS03120
etfA	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit	AZOBR_RS05475	AZOBR_RS16915
etfB	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit	AZOBR_RS05480	AZOBR_RS29740
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	AZOBR_RS01360
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	AZOBR_RS27000	AZOBR_RS23055
kdd	3,5-diaminohexanoate dehydrogenase
lat	L-lysine 6-aminotransferase	AZOBR_RS19630	AZOBR_RS03635
lhgD	L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)	AZOBR_RS33525
LHT	L-lysine transporter
lysDH	L-lysine 6-dehydrogenase	AZOBR_RS29980
lysL	L-lysine transporter LysL	AZOBR_RS13260
lysN	2-aminoadipate transaminase	AZOBR_RS12970	AZOBR_RS19630
lysP	L-lysine:H+ symporter LysP
patA	cadaverine aminotransferase	AZOBR_RS19590	AZOBR_RS19630
patD	5-aminopentanal dehydrogenase	AZOBR_RS09720	AZOBR_RS19635
Slc7a1	L-lysine transporter Slc7a1
ydiJ	(R)-2-hydroxyglutarate dehydrogenase	AZOBR_RS05770	AZOBR_RS29745

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