L-lysine catabolism in Pseudomonas fluorescens FW300-N2E3

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	AO353_16970	AO353_11995
hisM	L-lysine ABC transporter, permease component 1 (HisM)	AO353_16960	AO353_01530
hisQ	L-lysine ABC transporter, permease component 2 (HisQ)	AO353_16965	AO353_11990
hisP	L-lysine ABC transporter, ATPase component HisP	AO353_12000	AO353_16950
davB	L-lysine 2-monooxygenase	AO353_07420
davA	5-aminovaleramidase	AO353_07425	AO353_28330
davT	5-aminovalerate aminotransferase	AO353_11510	AO353_28215
davD	glutarate semialdehyde dehydrogenase	AO353_11505	AO353_28230
gcdG	succinyl-CoA:glutarate CoA-transferase	AO353_11105	AO353_23060
gcdH	glutaryl-CoA dehydrogenase	AO353_11100	AO353_20350
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	AO353_25675	AO353_00510
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	AO353_00510	AO353_27535
atoB	acetyl-CoA C-acetyltransferase	AO353_25685	AO353_27945
Alternative steps:
alr	lysine racemase	AO353_07155	AO353_09145
amaA	L-pipecolate oxidase	AO353_13335	AO353_24430
amaB	L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd)	AO353_13330	AO353_11505
amaD	D-lysine oxidase
bcd	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit	AO353_25680	AO353_25670
bgtB	L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)	AO353_25590
cadA	lysine decarboxylase	AO353_23560	AO353_13300
ctfA	butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit	AO353_27935
ctfB	butanoyl-CoA:acetoacetate CoA-transferase, beta subunit	AO353_27940
dpkA	1-piperideine-2-carboxylate reductase	AO353_23830	AO353_25185
etfA	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit	AO353_01230
etfB	butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit	AO353_01235
glaH	glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)
hglS	D-2-hydroxyglutarate synthase	AO353_21295
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	AO353_07745
kdd	3,5-diaminohexanoate dehydrogenase
lat	L-lysine 6-aminotransferase	AO353_28215	AO353_11510
lhgD	L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)
LHT	L-lysine transporter
lysDH	L-lysine 6-dehydrogenase
lysL	L-lysine transporter LysL	AO353_03465	AO353_20050
lysN	2-aminoadipate transaminase	AO353_28215	AO353_11510
lysP	L-lysine:H+ symporter LysP	AO353_24825	AO353_16120
patA	cadaverine aminotransferase	AO353_10500	AO353_15640
patD	5-aminopentanal dehydrogenase	AO353_04290	AO353_04265
Slc7a1	L-lysine transporter Slc7a1
ydiJ	(R)-2-hydroxyglutarate dehydrogenase	AO353_08505	AO353_21310

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.