L-lysine catabolism in Pseudomonas simiae WCS417

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	PS417_06415	PS417_01495
hisM	L-lysine ABC transporter, permease component 1 (HisM)	PS417_06405	PS417_01485
hisQ	L-lysine ABC transporter, permease component 2 (HisQ)	PS417_06410	PS417_01490
hisP	L-lysine ABC transporter, ATPase component HisP	PS417_01500	PS417_06395
davB	L-lysine 2-monooxygenase	PS417_25910
davA	5-aminovaleramidase	PS417_25915	PS417_04280
davT	5-aminovalerate aminotransferase	PS417_00900	PS417_23355
davD	glutarate semialdehyde dehydrogenase	PS417_00895	PS417_17840
gcdG	succinyl-CoA:glutarate CoA-transferase	PS417_00585	PS417_14920
gcdH	glutaryl-CoA dehydrogenase	PS417_00580	PS417_17015
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	PS417_13845	PS417_07575
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	PS417_07575	PS417_21215
atoB	acetyl-CoA C-acetyltransferase	PS417_10515	PS417_13855
Alternative steps:
alr	lysine racemase	PS417_25660	PS417_27695
amaA	L-pipecolate oxidase	PS417_02650	PS417_15495
amaB	L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd)	PS417_02645	PS417_00895
amaD	D-lysine oxidase	PS417_03805
bcd	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit	PS417_13850	PS417_13840
bgtB	L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)
cadA	lysine decarboxylase	PS417_12240	PS417_04005
ctfA	butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit	PS417_10525
ctfB	butanoyl-CoA:acetoacetate CoA-transferase, beta subunit	PS417_10520
dpkA	1-piperideine-2-carboxylate reductase	PS417_12515
etfA	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit	PS417_21295
etfB	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit	PS417_21300
glaH	glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)
hglS	D-2-hydroxyglutarate synthase	PS417_15555
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	PS417_26280	PS417_07250
kdd	3,5-diaminohexanoate dehydrogenase
lat	L-lysine 6-aminotransferase	PS417_00900	PS417_19505
lhgD	L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)
LHT	L-lysine transporter
lysDH	L-lysine 6-dehydrogenase
lysL	L-lysine transporter LysL	PS417_22325	PS417_22320
lysN	2-aminoadipate transaminase	PS417_23355	PS417_19025
lysP	L-lysine:H+ symporter LysP	PS417_05405	PS417_01505
patA	cadaverine aminotransferase	PS417_08025	PS417_21710
patD	5-aminopentanal dehydrogenase	PS417_05920	PS417_05945
Slc7a1	L-lysine transporter Slc7a1
ydiJ	(R)-2-hydroxyglutarate dehydrogenase	PS417_27035

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.