L-lysine catabolism in Pseudomonas putida KT2440

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 (35 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
argT	L-lysine ABC transporter, substrate-binding component ArgT	PP_3593	PP_0282
hisM	L-lysine ABC transporter, permease component 1 (HisM)	PP_3595	PP_0280
hisQ	L-lysine ABC transporter, permease component 2 (HisQ)	PP_3594	PP_0281
hisP	L-lysine ABC transporter, ATPase component HisP	PP_3597	PP_0283
davB	L-lysine 2-monooxygenase	PP_0383
davA	5-aminovaleramidase	PP_0382	PP_3846
davT	5-aminovalerate aminotransferase	PP_0214	PP_4108
davD	glutarate semialdehyde dehydrogenase	PP_0213	PP_4422
gcdG	succinyl-CoA:glutarate CoA-transferase	PP_0159	PP_3001
gcdH	glutaryl-CoA dehydrogenase	PP_0158	PP_4064
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	PP_2217	PP_3284
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	PP_2136	PP_3755
atoB	acetyl-CoA C-acetyltransferase	PP_2215	PP_4636
Alternative steps:
alr	lysine racemase	PP_3722	PP_0432
amaA	L-pipecolate oxidase	PP_5257
amaB	L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd)	PP_5258	PP_2694
amaD	D-lysine oxidase	PP_3596
bcd	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit	PP_2216	PP_3492
bgtB	L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)
cadA	lysine decarboxylase	PP_4140	PP_4871
ctfA	butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit	PP_3951	PP_3122
ctfB	butanoyl-CoA:acetoacetate CoA-transferase, beta subunit	PP_3123	PP_3952
dpkA	1-piperideine-2-carboxylate reductase	PP_3591	PP_4431
etfA	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit	PP_4201
etfB	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit	PP_4202
glaH	glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)	PP_2909
hglS	D-2-hydroxyglutarate synthase	PP_5260
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	PP_0303
kdd	3,5-diaminohexanoate dehydrogenase
lat	L-lysine 6-aminotransferase	PP_0214	PP_4223
lhgD	L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)	PP_2910
LHT	L-lysine transporter
lysDH	L-lysine 6-dehydrogenase
lysL	L-lysine transporter LysL	PP_1002	PP_1003
lysN	2-aminoadipate transaminase	PP_4108	PP_0214
lysP	L-lysine:H+ symporter LysP	PP_3727	PP_0660
patA	cadaverine aminotransferase	PP_4223	PP_4481
patD	5-aminopentanal dehydrogenase	PP_1481	PP_2801
Slc7a1	L-lysine transporter Slc7a1
ydiJ	(R)-2-hydroxyglutarate dehydrogenase	PP_4493	PP_5154

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.