L-lysine catabolism in Caulobacter crescentus NA1000

GapMind for catabolism of small carbon sources

L-lysine catabolism in Caulobacter crescentus NA1000

Best path

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 (27 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
lysP	L-lysine:H+ symporter LysP
lat	L-lysine 6-aminotransferase	CCNA_03233	CCNA_02326
amaB	L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd)	CCNA_01274	CCNA_00865
lysN	2-aminoadipate transaminase	CCNA_01603	CCNA_02244
hglS	D-2-hydroxyglutarate synthase
ydiJ	(R)-2-hydroxyglutarate dehydrogenase	CCNA_03500
Alternative steps:
alr	lysine racemase
amaA	L-pipecolate oxidase
amaD	D-lysine oxidase
argT	L-lysine ABC transporter, substrate-binding component ArgT	CCNA_01508
atoB	acetyl-CoA C-acetyltransferase	CCNA_00820	CCNA_00544
bcd	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit	CCNA_01412	CCNA_02254
bgtB	L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)
cadA	lysine decarboxylase	CCNA_00365	CCNA_01372
ctfA	butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit	CCNA_00206	CCNA_02488
ctfB	butanoyl-CoA:acetoacetate CoA-transferase, beta subunit	CCNA_02489	CCNA_00207
davA	5-aminovaleramidase	CCNA_00871
davB	L-lysine 2-monooxygenase
davD	glutarate semialdehyde dehydrogenase	CCNA_03242	CCNA_03243
davT	5-aminovalerate aminotransferase	CCNA_00620	CCNA_02326
dpkA	1-piperideine-2-carboxylate reductase
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	CCNA_00006	CCNA_01794
etfA	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit	CCNA_00763
etfB	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit	CCNA_00764
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	CCNA_00123	CCNA_03293
gcdG	succinyl-CoA:glutarate CoA-transferase	CCNA_03677	CCNA_02410
gcdH	glutaryl-CoA dehydrogenase	CCNA_02254	CCNA_01412
glaH	glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)
hisM	L-lysine ABC transporter, permease component 1 (HisM)	CCNA_01507
hisP	L-lysine ABC transporter, ATPase component HisP	CCNA_01506	CCNA_02751
hisQ	L-lysine ABC transporter, permease component 2 (HisQ)	CCNA_01507
kal	3-aminobutyryl-CoA deaminase
kamA	L-lysine 2,3-aminomutase	CCNA_00753
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
kdd	3,5-diaminohexanoate dehydrogenase
lhgD	L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)	CCNA_03278
LHT	L-lysine transporter
lysDH	L-lysine 6-dehydrogenase
lysL	L-lysine transporter LysL
patA	cadaverine aminotransferase	CCNA_02326	CCNA_00620
patD	5-aminopentanal dehydrogenase	CCNA_03243	CCNA_03695
Slc7a1	L-lysine transporter Slc7a1	CCNA_01242	CCNA_00435

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