L-lysine catabolism in Paraburkholderia bryophila 376MFSha3.1

GapMind for catabolism of small carbon sources

L-lysine catabolism in Paraburkholderia bryophila 376MFSha3.1

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 (33 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
argT	L-lysine ABC transporter, substrate-binding component ArgT	H281DRAFT_00224	H281DRAFT_03659
hisM	L-lysine ABC transporter, permease component 1 (HisM)	H281DRAFT_00222	H281DRAFT_06475
hisQ	L-lysine ABC transporter, permease component 2 (HisQ)	H281DRAFT_00223	H281DRAFT_06474
hisP	L-lysine ABC transporter, ATPase component HisP	H281DRAFT_05293	H281DRAFT_06476
davB	L-lysine 2-monooxygenase
davA	5-aminovaleramidase	H281DRAFT_03146	H281DRAFT_05434
davT	5-aminovalerate aminotransferase	H281DRAFT_03179	H281DRAFT_06478
davD	glutarate semialdehyde dehydrogenase	H281DRAFT_03178	H281DRAFT_03540
gcdG	succinyl-CoA:glutarate CoA-transferase	H281DRAFT_04444	H281DRAFT_01169
gcdH	glutaryl-CoA dehydrogenase	H281DRAFT_04737	H281DRAFT_01204
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	H281DRAFT_05725	H281DRAFT_02514
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	H281DRAFT_00361	H281DRAFT_04625
atoB	acetyl-CoA C-acetyltransferase	H281DRAFT_00852	H281DRAFT_00857
Alternative steps:
alr	lysine racemase	H281DRAFT_00589
amaA	L-pipecolate oxidase	H281DRAFT_02574	H281DRAFT_06337
amaB	L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd)	H281DRAFT_01833	H281DRAFT_03540
amaD	D-lysine oxidase	H281DRAFT_05881	H281DRAFT_03160
bcd	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit	H281DRAFT_06133	H281DRAFT_02091
bgtB	L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)
cadA	lysine decarboxylase	H281DRAFT_00160	H281DRAFT_04542
ctfA	butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit	H281DRAFT_04495	H281DRAFT_01597
ctfB	butanoyl-CoA:acetoacetate CoA-transferase, beta subunit	H281DRAFT_04496	H281DRAFT_01596
dpkA	1-piperideine-2-carboxylate reductase	H281DRAFT_05357	H281DRAFT_02928
etfA	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit	H281DRAFT_04285	H281DRAFT_03367
etfB	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit	H281DRAFT_01168	H281DRAFT_03903
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	H281DRAFT_03174	H281DRAFT_00641
kdd	3,5-diaminohexanoate dehydrogenase
lat	L-lysine 6-aminotransferase	H281DRAFT_03179	H281DRAFT_02621
lhgD	L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)	H281DRAFT_02167
LHT	L-lysine transporter
lysDH	L-lysine 6-dehydrogenase	H281DRAFT_05221
lysL	L-lysine transporter LysL
lysN	2-aminoadipate transaminase	H281DRAFT_00271	H281DRAFT_03179
lysP	L-lysine:H+ symporter LysP	H281DRAFT_04042	H281DRAFT_01668
patA	cadaverine aminotransferase	H281DRAFT_02621	H281DRAFT_06478
patD	5-aminopentanal dehydrogenase	H281DRAFT_03016	H281DRAFT_02464
Slc7a1	L-lysine transporter Slc7a1	H281DRAFT_02180
ydiJ	(R)-2-hydroxyglutarate dehydrogenase	H281DRAFT_02585	H281DRAFT_04480

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