L-lysine catabolism in Pseudomonas fluorescens FW300-N2E2

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	Pf6N2E2_2958	Pf6N2E2_3856
hisM	L-lysine ABC transporter, permease component 1 (HisM)	Pf6N2E2_2960	Pf6N2E2_3858
hisQ	L-lysine ABC transporter, permease component 2 (HisQ)	Pf6N2E2_2959	Pf6N2E2_3857
hisP	L-lysine ABC transporter, ATPase component HisP	Pf6N2E2_2962	Pf6N2E2_3855
davB	L-lysine 2-monooxygenase	Pf6N2E2_4778
davA	5-aminovaleramidase	Pf6N2E2_4777	Pf6N2E2_3172
davT	5-aminovalerate aminotransferase	Pf6N2E2_4013	Pf6N2E2_373
davD	glutarate semialdehyde dehydrogenase	Pf6N2E2_4014	Pf6N2E2_368
gcdG	succinyl-CoA:glutarate CoA-transferase	Pf6N2E2_4035	Pf6N2E2_3139
gcdH	glutaryl-CoA dehydrogenase	Pf6N2E2_4036	Pf6N2E2_2191
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	Pf6N2E2_1147	Pf6N2E2_1834
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	Pf6N2E2_2290	Pf6N2E2_1922
atoB	acetyl-CoA C-acetyltransferase	Pf6N2E2_2113	Pf6N2E2_1145
Alternative steps:
alr	lysine racemase	Pf6N2E2_4836	Pf6N2E2_4393
amaA	L-pipecolate oxidase	Pf6N2E2_3581
amaB	L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd)	Pf6N2E2_3582	Pf6N2E2_4014
amaD	D-lysine oxidase
bcd	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit	Pf6N2E2_1146	Pf6N2E2_1148
bgtB	L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)	Pf6N2E2_1799
cadA	lysine decarboxylase	Pf6N2E2_3589	Pf6N2E2_3334
ctfA	butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit	Pf6N2E2_2111
ctfB	butanoyl-CoA:acetoacetate CoA-transferase, beta subunit	Pf6N2E2_2112
dpkA	1-piperideine-2-carboxylate reductase	Pf6N2E2_1089
etfA	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit	Pf6N2E2_5984
etfB	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit	Pf6N2E2_5983
glaH	glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)
hglS	D-2-hydroxyglutarate synthase	Pf6N2E2_134
kal	3-aminobutyryl-CoA deaminase
kamA	L-lysine 2,3-aminomutase	Pf6N2E2_2163
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	Pf6N2E2_4692
kdd	3,5-diaminohexanoate dehydrogenase
lat	L-lysine 6-aminotransferase	Pf6N2E2_373	Pf6N2E2_4013
lhgD	L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)	Pf6N2E2_261
LHT	L-lysine transporter
lysDH	L-lysine 6-dehydrogenase
lysL	L-lysine transporter LysL	Pf6N2E2_2907	Pf6N2E2_2906
lysN	2-aminoadipate transaminase	Pf6N2E2_5269	Pf6N2E2_1496
lysP	L-lysine:H+ symporter LysP	Pf6N2E2_4959	Pf6N2E2_5459
patA	cadaverine aminotransferase	Pf6N2E2_5326	Pf6N2E2_2395
patD	5-aminopentanal dehydrogenase	Pf6N2E2_3131	Pf6N2E2_3126
Slc7a1	L-lysine transporter Slc7a1
ydiJ	(R)-2-hydroxyglutarate dehydrogenase	Pf6N2E2_3933	Pf6N2E2_1497

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.