Definition of L-lysine catabolism

As rules and steps, or see full text

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

Steps

lysP: L-lysine:H+ symporter LysP

• Curated sequence CH_003129: lysine-specific permease. Lysine:H+ symporter. Forms a stable complex with CadC to allow lysine-dependent adaptation to acidic stress (Rauschmeier et al. 2013). The Salmonella orthologue is 95% identical to the E. coli protein and is highly specific for Lysine. Residues involved in lysine binding have been identified. lysine:H⁺ symporter. lysine:H⁺ symporter
• Curated sequence CH_091040: lysine-specific permease. Lysine-specific permease. Lysine permease of 611 aas and 13 putative TMSs, Lyp1
• Curated sequence CH_091257: S-adenosylmethionine permease SAM3. S-adenosylmethionine permease SAM3; S-adenosylmethionine metabolism protein 3. S-adenosylmethionine uptake permease, SAM3 (also takes up polyamines, glutamate, lysine and the toxic S-adenosylmethionine analogue sinefungin)
• Curated sequence CH_091412: uncharacterized amino-acid permease C869.11. The basic amino acid (canavanine sensitivity) transporter, Cat1
• Curated sequence A0A1D8PPG4: Probable lysine/arginine permease CAN3; Basic amino acids permease CAN3
• Curated sequence A0A1D8PPI5: Lysine/arginine permease CAN1; Basic amino acids permease CAN1
• Curated sequence A2RNZ6: Lysine permease LysP
• Curated sequence Q59WU0: Probable lysine/arginine permease CAN2; Basic amino acids permease CAN2
• Curated sequence K7VV21: The lysine specific transporter, LysP of 488 aas and 12 TMSs
• Curated sequence P43059: The high affinity basic amino acid (Arg, Lys, His) transporter, Can1
• Total: 10 characterized proteins

LHT: L-lysine transporter

• Curated sequence Q9FKS8: Lysine histidine transporter 1. Lysine/histidine transporter, LHT1
• Curated sequence Q9LRB5: Lysine histidine transporter 2; AtLHT2; Amino acid transporter-like protein 2. Lysine/histidine transporter 2 (AtLHT2) (Amino acid transporter-like protein 2)
• Curated sequence Q9SX98: Lysine histidine transporter-like 8; Amino acid transporter-like protein 1. Lysine histidine transporter-like 8 (Amino acid transporter-like protein 1)
• Curated sequence Q84WE9: Lysine-Histidine Transporter-7 (LHT7) found in mature pollen (Bock et al., 2006) (most like 2.A.18.2.2; 30% identity)
• Total: 4 characterized proteins

Slc7a1: L-lysine transporter Slc7a1

• Curated sequence CH_091036: Cationic amino acid transporter 3. Cationic amino acid transporter 3; CAT-3; CAT3; Cationic amino acid transporter y+; Solute carrier family 7 member 3. The brain L-cationic (Arg, Lys, Orn, 2,4-diamino-n-butyrate) transporter, CAT3 (capacity of trans-stimulation by internal Arg)
• Curated sequence CH_091271: low affinity cationic amino acid transporter 2. Low affinity basic amino acid transporter (CAT2) (T-cell early activation protein (TEA)) (transports arginine, lysine and ornithine; Na+-independent)
• Curated sequence CH_091324: high affinity cationic amino acid transporter 1. High affinity cationic amino acid transporter 1; CAT-1; CAT1; Ecotropic retroviral leukemia receptor; Ecotropic retrovirus receptor; ERR; Solute carrier family 7 member 1; System Y+ basic amino acid transporter. System Y+ high affinity basic amino acid transporter (CAT1) (ecotropic retrovival leukemia virus receptor (ERR)) (transports arginine, lysine and ornithine; Na+-independent)
• Total: 3 characterized proteins

lysL: L-lysine transporter LysL

• Curated sequence CH_019644: L-lysine transport protein. Lysine permease
• Total: 1 characterized proteins

argT: L-lysine ABC transporter, substrate-binding component ArgT

• Curated sequence CH_003045: lysine/arginine/ornithine ABC transporter, periplasmic lysine/arginine/ornithine-binding protein ArgT. Lysine/arginine/ornithine-binding periplasmic protein; LAO-binding protein
• Curated sequence P09551: ArgT aka B2310, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter periplasmic binding protein (EC 7.4.2.1)
• Curated sequence Q9HU31: Amino acid (Lysine/arginine/ornithine/histidine/octopine) ABC transporter periplasmic binding protein, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
• Curated sequence AO356_05495: ABC transporter for L-Lysine, periplasmic substrate-binding component
• Curated sequence AO356_09900: ABC transporter for L-Lysine, periplasmic substrate-binding component
• Curated sequence Pf6N2E2_2958: ABC transporter for L-Lysine, periplasmic substrate-binding component
• UniProt sequence Q92PA9: SubName: Full=Putative amino-acid binding periplasmic protein {ECO:0000313|EMBL:CAC46449.1};
• UniProt sequence Q88GX4: SubName: Full=Amino acid ABC transporter, periplasmic binding protein {ECO:0000313|EMBL:AAN69193.1};
• Comment: In E. coli and Salmonella, the ABC transporter has a lysine/arginine specific binding protein (argT), two permease subunits (hisQM, which are similar to each other), and an ATPase subunit (hisP). Pseudomonas aeruginosa has a homologous lysine transporter, PA5152-PA5155, as do various strains of Pseudomonas fluorescens. In P. putida, a similar system was identified using fitness data (argT = PP_3593 = Q88GX4; hisQ = PP_3594 = Q88GX3; hisM = PP_3595 = Q88GX2; hisP = PP_3597 = Q88GX0). In S. meliloti, a similar substrate-binding protein was identified using fitness data (SMc00140 = Q92PA9), but the ATPase subunit was not found (it might be shared with other systems).
• Total: 8 characterized proteins

hisM: L-lysine ABC transporter, permease component 1 (HisM)

• Curated sequence P0A2I7: Histidine transport system permease protein HisM. Histidine transport system permease protein HisM aka STM2352, component of Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium
• Curated sequence P0AEU3: Histidine transport system permease protein HisM. Histidine transport system permease protein HisM, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter / histidine ABC transporter, membrane subunit HisM (EC 7.4.2.1)
• Curated sequence Q9HU29: Amino acid (Lysine/arginine/ornithine/histidine/octopine) ABC transporter membrane protein, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
• Curated sequence AO356_05505: ABC transporter for L-Lysine, permease component 2
• Curated sequence AO356_09910: ABC transporter for L-Lysine, permease component 2
• Curated sequence Pf6N2E2_2960: ABC transporter for L-Lysine, permease component 2
• UniProt sequence Q88GX2: SubName: Full=Amino acid ABC transporter, membrane protein {ECO:0000313|EMBL:AAN69195.1};
• Total: 7 characterized proteins

hisQ: L-lysine ABC transporter, permease component 2 (HisQ)

• Curated sequence P0A2I9: Histidine transport system permease protein HisQ. Histidine transport system permease protein HisQ aka STM2353, component of Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium
• Curated sequence P52094: Histidine transport system permease protein HisQ. Histidine transport system permease protein HisQ, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter / histidine ABC transporter, membrane subunit HisQ (EC 7.4.2.1)
• Curated sequence Q9HU30: Probable permease of ABC transporter, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
• Curated sequence AO356_05500: ABC transporter for L-Lysine, permease component 1
• Curated sequence AO356_09905: ABC transporter for L-Lysine, permease component 1
• Curated sequence Pf6N2E2_2959: ABC transporter for L-Lysine, permease component 1
• UniProt sequence Q88GX3: SubName: Full=Amino acid ABC transporter, membrane protein {ECO:0000313|EMBL:AAN69194.1};
• Total: 7 characterized proteins

hisP: L-lysine ABC transporter, ATPase component HisP

• Curated sequence CH_003210: histidine transport ATP-binding protein hisP. Histidine transport ATP-binding protein HisP, component of Histidine/Arginine/Lysine (basic amino acid) uptake porter, HisJ/ArgT/HisP/HisM/HisQ [R, R, C, M, M, respectively] (Gilson et al. 1982). HisJ binds L-His (preferred), but 1-methyl-L-His and 3-methyl-L-His also bind, while the dipeptide carnosine binds weakly; D-histidine and the histidine degradation products, histamine, urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post-translationally modified methylated Arg-analogs also bind with the exception of symmetric dimethylated-L-Arg. L-Lys and L-Orn show weaker interactions with HisJ and methylated and acetylated Lys variants show poor binding.The carboxylate groups of these amino acids and their variants are essential. lysine/arginine/ornithine ABC transporter / histidine ABC transporter, ATP binding subunit (EC 7.4.2.1)
• Curated sequence P02915: Histidine transport ATP-binding protein HisP. histidine transport atp-binding protein hisp. HisP aka STM2351, component of Histidine/arginine/lysine/ornithine porter (Heuveling et al. 2014). In contrast to some homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica Typhimurium
• Curated sequence P73721: BgtA aka SLR1735, component of Arginine/lysine/histidine/glutamine porter
• Curated sequence Q9HU32: Probable ATP-binding component of ABC transporter, component of Amino acid transporter, PA5152-PA5155. Probably transports numerous amino acids including lysine, arginine, histidine, D-alanine and D-valine (Johnson et al. 2008). Regulated by ArgR
• Curated sequence AO356_05515: ABC transporter for L-Lysine, ATPase component
• Curated sequence AO356_09895: ABC transporter for L-Lysine, ATPase component
• Curated sequence Pf6N2E2_2962: ABC transporter for L-Lysine, ATPase component
• UniProt sequence Q88GX0: SubName: Full=Amino-acid ABC transporter, ATP-binding protein {ECO:0000313|EMBL:AAN69197.1};
• Total: 8 characterized proteins

bgtB: L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)

• Curated sequence P73544: BgtB aka GLNH aka SLL1270, component of Arginine/lysine/histidine/glutamine porter
• Curated sequence Q8YSA2: Basic amino acid uptake transporter, BgtAB
• Comment: In Synechocystis, there is just one permease component fused to the substrate-binding component. The fusion protein is known as BgtB or BgtAB; BgtA is the hisP-like ATPase component.
• Total: 2 characterized proteins

atoB: acetyl-CoA C-acetyltransferase

• Curated proteins or TIGRFams with EC 2.3.1.9
• Ignore hits to items matching 2.3.1.16 when looking for 'other' hits
• Ignore hits to P07256 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (EC 2.3.1.9). Cytochrome b-c1 complex subunit 1, mitochondrial; Complex III subunit 1; Core protein I; Ubiquinol-cytochrome c oxidoreductase core protein 1; Ubiquinol-cytochrome c reductase 44 kDa protein)
• Ignore hits to I3R3D0 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
• Ignore hits to I3RA71 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
• Ignore hits to items matching similar to acetyl-CoA acetyltransferase when looking for 'other' hits
• Comment: Produces two acetyl-CoA from acetoacetyl-CoA and CoA. EC 2.3.1.16 describes a broader range of beta-ketothiolases. This enzyme is usually homomeric, but I3R3D0 and I3RA71 are non-catalytic subunits of an enzyme from Haloferax mediterranei that also contains a "normal" catalytic subunit (I3R3D1, I3RA72). Inclusion of P07256 was an error in BRENDA. And CharProtDB includes an odd annotation of the form "similar to acetyl-CoA acetyltransferase"
• Total: 36 characterized proteins

gcdH: glutaryl-CoA dehydrogenase

• Curated proteins or TIGRFams with EC 1.3.8.6
• Total: 6 characterized proteins

ech: (S)-3-hydroxybutanoyl-CoA hydro-lyase

• Curated proteins or TIGRFams with EC 4.2.1.150
• Ignore hits to Q97MS7 when looking for 'other' hits (short-chain-enoyl-CoA hydratase (EC 4.2.1.150))
• Curated sequence BPHYT_RS17335: trans-2,3-dehydroadipyl-CoA hydratase (EC 4.2.1.17)
• Curated sequence GFF2389: Enoyl-CoA hydratase [valine degradation] (EC 4.2.1.17)
• Ignore hits to items matching 4.2.1.17 when looking for 'other' hits
• Comment: Psest_2437 (GFF2389) is the enoyl-CoA hydrotase for both isoleucine and valine degradation, which implies that (S)-3-hydroxybutanoyl-CoA is a substrate. Q97MS7 is misannotated in BRENDA. BPHYT_RS17335 was misannotated as paaF; it is very similar to the ech H16_A3307, which is a different explanation for its role in phenylacetate utilization. Short-chain enoyl-CoA hydratases are sometimes given EC 4.2.1.17 instead, so those are ignored.
• Total: 8 characterized proteins

fadB: (S)-3-hydroxybutanoyl-CoA dehydrogenase

• Curated proteins or TIGRFams with EC 1.1.1.35
• Ignore hits to GFF1550 when looking for 'other' hits (Enoyl-CoA hydratase (EC 4.2.1.17))
• Comment: HP15_1512 (GFF1550) is annotated as enoyl-CoA hydratase but likely does this as well
• Total: 36 characterized proteins

glaH: glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)

• Curated proteins or TIGRFams with EC 1.14.11.64
• Total: 2 characterized proteins

lhgD: L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)

• Curated proteins or TIGRFams with EC 1.1.5.13
• Curated sequence G1G01-3089-MONOMER: (S)-2-hydroxyglutarate oxidase
• Curated proteins or TIGRFams with EC 1.1.99.2
• Comment: As discussed in the MetaCyc page for lhgO (G1G01-3089-MONOMER), there is some controversy as to whether the E. coli enzyme (lhgD) uses quinone or oxygen as its acceptor; the Pseudomonas protein (G1G01-3089-MONOMER) does use oxygen.
• Total: 4 characterized proteins

gcdG: succinyl-CoA:glutarate CoA-transferase

• Curated proteins or TIGRFams with EC 2.8.3.13
• Total: 2 characterized proteins

davT: 5-aminovalerate aminotransferase

• Curated proteins or TIGRFams with EC 2.6.1.48
• Ignore hits to MONOMER-11537 when looking for 'other' hits (4-aminobutyrate transaminase subunit (EC 2.6.1.19))
• Ignore hits to Q0K2K2 when looking for 'other' hits (4-aminobutyrate-2-oxoglutarate transaminase (EC 2.6.1.19). 4-aminobutyrate aminotransferase monomer (EC 2.6.1.19))
• Comment: Ignore some very-similar 4-aminobutyrate transaminases
• Total: 6 characterized proteins

davD: glutarate semialdehyde dehydrogenase

• Curated proteins or TIGRFams with EC 1.2.1.20
• Ignore hits to AO353_11505 when looking for 'other' hits (succinate-semialdehyde dehydrogenase (EC 1.2.1.16))
• Ignore hits to MONOMER-15736 when looking for 'other' hits (NAD(P)-dependent succinate-semialdehyde dehydrogenase (EC 1.2.1.16))
• Curated sequence Q9I6M5: Glutarate-semialdehyde dehydrogenase; EC 1.2.1.-. glutarate semialdehyde dehydrogenase
• Ignore hits to P25526 when looking for 'other' hits (succinate-semialdehyde dehydrogenase (NADP+) (EC 1.2.1.79). succinate-semialdehyde dehydrogenase [NAD(P)+]; EC 1.2.1.16. Succinate-semialdehyde dehydrogenase [NADP(+)] GabD; SSDH; Glutarate-semialdehyde dehydrogenase; EC 1.2.1.79; EC 1.2.1.-. succinate-semialdehyde dehydrogenase (NADP⁺) GabD (EC 1.2.1.79). succinate-semialdehyde dehydrogenase (NADP⁺) GabD (EC 1.2.1.79))
• Ignore hits to MONOMER-20455 when looking for 'other' hits (succinate-semialdehyde dehydrogenase (NAD⁺) (EC 1.2.1.24))
• Ignore hits to 200453 when looking for 'other' hits (succinate-semialdehyde dehydrogenase (NADP+) [EC: 1.2.1.16])
• Comment: Ignore some very-similar succinate-semialdehyde dehydrogenases
• Total: 3 characterized proteins

lysN: 2-aminoadipate transaminase

• Curated proteins or TIGRFams with EC 2.6.1.39
• Ignore hits to Q06191 when looking for 'other' hits (Aspartate aminotransferase; AAT; AspAT; Transaminase A; EC 2.6.1.1)
• Comment: Q06191 is very similar to SMc04386 (P58350), which is specifically important for lysine utilization.
• Total: 8 characterized proteins

hglS: D-2-hydroxyglutarate synthase

• Curated sequence PP_5260: 2-oxoadipate decarboxylase/hydroxylase (2-hydroxyglutarate synthase)
• Curated sequence AO356_01105: putative hydrolase, required for lysine catabolism
• Curated sequence SMc04383: putative hydrolase, required for lysine catabolism
• Curated sequence G6738-MONOMER: DUF1338 domain-containing protein YdcJ
• Comment: PP_5260 was shown to be form D-2-hydroxyglutarate (link). Homologous proteins that are specifically important for L-lysine utilization are also included. The E. coli homolog (ydcJ, G6738-MONOMER) also has this activity, see PMC7286885.
• Total: 4 characterized proteins

ydiJ: (R)-2-hydroxyglutarate dehydrogenase

• Curated proteins or TIGRFams with EC 1.1.99.39
• Curated proteins or TIGRFams with EC 1.1.99.40
• Curated sequence PP_4493: 2-hydroxyglutarate oxidase (EC 1.1.3.15)
• UniProt sequence Q92L08: SubName: Full=Putative oxidoreductase {ECO:0000313|EMBL:CAC47868.1};
• Comment: PP_4493 was misannotated as EC 1.1.3.15, which acts on (S)-2-hydroxyglutarate. The E. coli homolog (ydiJ, link) does not seem to be characterized. SMc04384 (Q92L08) was identified using fitness data.
• Total: 6 characterized proteins

cadA: lysine decarboxylase

• Curated proteins or TIGRFams with EC 4.1.1.18
• Ignore hits to A0A0H3H393 when looking for 'other' hits (lysine decarboxylase (EC 4.1.1.18))
• Comment: A0A0H3H393 is very similar to E. coli diaminopimelate decarboxylase and could not access the paper about it, so do not trust it.
• Total: 11 characterized proteins

patA: cadaverine aminotransferase

• Curated sequence G7596-MONOMER: putrescine-2-oxoglutarate transaminase (EC 2.6.1.82). Putrescine aminotransferase; PAT; PATase; Cadaverine transaminase; Putrescine transaminase; Putrescine--2-oxoglutaric acid transaminase; Putrescine:2-OG aminotransferase; EC 2.6.1.82; EC 2.6.1.-. putrescine aminotransferase (EC 2.6.1.29). putrescine aminotransferase (EC 2.6.1.29)
• Comment: E. coli's putrescine aminotransferase (patA) is known to carry out this reaction as well. I could not identify any evidence of other proteins that carry out this reaction (although it seems likely that other putrescine aminotransferases could).
• Total: 1 characterized proteins

patD: 5-aminopentanal dehydrogenase

• Curated sequence P77674: aminobutyraldehyde dehydrogenase (EC 1.2.1.19). Gamma-aminobutyraldehyde dehydrogenase; ABALDH; 1-pyrroline dehydrogenase; 4-aminobutanal dehydrogenase; 5-aminopentanal dehydrogenase; EC 1.2.1.19; EC 1.2.1.-. γ-aminobutyraldehyde dehydrogenase (EC 1.2.1.19). γ-aminobutyraldehyde dehydrogenase (EC 1.2.1.19)
• Ignore hits to items matching 1.2.1.19 when looking for 'other' hits
• Comment: E. coli 4-aminobutanal dehydrogenase (patD, P77674) is known to carry out this reaction. It seems likely that other members of EC 1.2.1.19 (4-aminobutanal dehydrogenase) would perform it as well.
• Total: 1 characterized proteins

davB: L-lysine 2-monooxygenase

• Curated proteins or TIGRFams with EC 1.13.12.2
• Total: 7 characterized proteins

davA: 5-aminovaleramidase

• Curated proteins or TIGRFams with EC 3.5.1.30
• Total: 6 characterized proteins

alr: lysine racemase

• Curated proteins or TIGRFams with EC 5.1.1.5
• Ignore hits to items matching 5.1.1.10 when looking for 'other' hits
• Comment: Some lysine racemases are very similar to broad-specificity amino acid racemases (EC 5.1.1.10)
• Total: 5 characterized proteins

amaD: D-lysine oxidase

• Curated proteins or TIGRFams with EC 1.4.3.3
• Ignore hits to P80340 when looking for 'other' hits (50S ribosomal protein L34. D-amino-acid oxidase (EC 1.4.3.3))
• Comment: The ribosomal protein P80340 is misannotated in BRENDA
• Total: 19 characterized proteins

dpkA: 1-piperideine-2-carboxylate reductase

• Curated proteins or TIGRFams with EC 1.5.1.1
• Curated proteins or TIGRFams with EC 1.5.1.21
• Total: 10 characterized proteins

amaA: L-pipecolate oxidase

• Curated proteins or TIGRFams with EC 1.5.3.7
• Total: 4 characterized proteins

amaB: L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd)

• Curated proteins or TIGRFams with EC 1.2.1.31
• Ignore hits to Q4L235 when looking for 'other' hits (Beta-alanine-activating enzyme; Acyl-CoA synthetase family member 4; Protein NRPS998; EC 6.2.1.-. L-aminoadipate-semialdehyde dehydrogenase (EC 1.2.1.31))
• Do not include HMM TIGR03443 (when considering EC numbers)
• Ignore hits to P83402 when looking for 'other' hits (Alpha-aminoadipic semialdehyde dehydrogenase; Alpha-AASA dehydrogenase; Aldehyde dehydrogenase family 7 member A1; Antiquitin-1; Delta1-piperideine-6-carboxylate dehydrogenase; P6c dehydrogenase; EC 1.2.1.31)
• Ignore hits to P84463 when looking for 'other' hits (Alpha-aminoadipic semialdehyde dehydrogenase; Alpha-AASA dehydrogenase; Aldehyde dehydrogenase family 7 member A1; Antiquitin-1; Delta1-piperideine-6-carboxylate dehydrogenase; P6c dehydrogenase; EC 1.2.1.31)
• Curated sequence MONOMER-12387: Δ¹-piperideine-6-carboxylate dehydrogenase
• UniProt sequence Q88CC3: SubName: Full=L-piperidine-6-carboxylate dehydrogenase {ECO:0000313|EMBL:AAN70823.1}; EC=1.2.1.21 {ECO:0000313|EMBL:AAN70823.1};
• UniProt sequence Q92L07: SubName: Full=Putative aldehyde dehydrogenase transmembrane protein {ECO:0000313|EMBL:CAC47869.1}; EC=1.2.1.3 {ECO:0000313|EMBL:CAC47869.1};
• Comment: Q4L235 is misannotated in BRENDA. TIGR03443 hits both amaB and the ATP-hydrolyzing L-2-aminoadipate reductase. P83402 and P84463 are short sequence fragments. In MetaCyc, MONOMER-20455 is annotated as performing this reaction but was not given this EC number. PP_5258 (Q88CC3) is in a newer version of metacyc. SMc04385 (Q92L07) was identified using fitness data.
• Total: 9 characterized proteins

lat: L-lysine 6-aminotransferase

• Curated proteins or TIGRFams with EC 2.6.1.36
• Total: 1 HMMs and 6 characterized proteins

lysDH: L-lysine 6-dehydrogenase

• Curated proteins or TIGRFams with EC 1.4.1.18
• Total: 4 characterized proteins

kamA: L-lysine 2,3-aminomutase

• Curated proteins or TIGRFams with EC 5.4.3.2
• Total: 1 HMMs and 8 characterized proteins

kamD: L-beta-lysine 5,6-aminomutase, alpha subunit

• Curated sequence Q8RHX7: lysine 5,6-aminomutase (subunit 2/2) (EC 5.4.3.3). Lysine 5,6-aminomutase alpha subunit; 5,6-LAM; D-lysine 5,6-aminomutase alpha subunit; L-beta-lysine 5,6-aminomutase alpha subunit; EC 5.4.3.3. L-β-lysine-5,6-aminomutase α subunit (EC 5.4.3.3)
• Curated sequence E3PRJ5: Lysine 5,6-aminomutase alpha subunit; 5,6-LAM; D-lysine 5,6-aminomutase alpha subunit; L-beta-lysine 5,6-aminomutase alpha subunit; EC 5.4.3.3. lysine 5,6-aminomutase (subunit 2/2) (EC 5.4.3.3)
• Total: 2 characterized proteins

kamE: L-beta-lysine 5,6-aminomutase, beta subunit

• Curated sequence Q8RHX8: lysine 5,6-aminomutase (subunit 1/2) (EC 5.4.3.3). Lysine 5,6-aminomutase beta subunit; 5,6-LAM; D-lysine 5,6-aminomutase beta subunit; L-beta-lysine 5,6-aminomutase beta subunit; EC 5.4.3.3. L-β-lysine-5,6-aminomutase β subunit (EC 5.4.3.3)
• Curated sequence E3PRJ4: Lysine 5,6-aminomutase beta subunit; 5,6-LAM; D-lysine 5,6-aminomutase beta subunit; L-beta-lysine 5,6-aminomutase beta subunit; EC 5.4.3.3. lysine 5,6-aminomutase (subunit 1/2) (EC 5.4.3.3)
• Total: 2 characterized proteins

kdd: 3,5-diaminohexanoate dehydrogenase

• Curated proteins or TIGRFams with EC 1.4.1.11
• Total: 1 characterized proteins

kce: (S)-5-amino-3-oxohexanoate cleavage enzyme

• Curated proteins or TIGRFams with EC 2.3.1.247
• Total: 2 characterized proteins

kal: 3-aminobutyryl-CoA deaminase

• Curated proteins or TIGRFams with EC 4.3.1.14
• Total: 1 characterized proteins

bcd: butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit

• Curated sequence D2RL84: butanoyl-CoA dehydrogenase (NAD+, ferredoxin) (subunit 1/3) (EC 1.3.1.109); short-chain acyl-CoA dehydrogenase (subunit 1/2) (EC 1.3.8.1)
• Curated sequence Q18AQ1: butanoyl-CoA dehydrogenase (NAD+, ferredoxin) (subunit 3/3) (EC 1.3.1.109); short-chain acyl-CoA dehydrogenase (EC 1.3.8.1)
• Ignore hits to D9TQ00 when looking for 'other' hits (butanal dehydrogenase (EC 1.2.1.57))
• Curated sequence P52042: butyryl-CoA dehydrogenase; EC 1.3.99.2. Acyl-CoA dehydrogenase, short-chain specific; Butyryl-CoA dehydrogenase; SCAD; EC 1.3.8.1. butyryl-CoA dehydrogenase (EC 1.3.8.1)
• Curated sequence MONOMER-11937: butyryl-CoA dehydrogenase; EC 1.3.99.2. butyryl-CoA dehydrogenase subunit (EC 1.3.8.1)
• Curated sequence MONOMER-13470: butyryl-CoA dehydrogenase (EC 1.3.8.1)
• Comment: D9TQ00 is probably misannotated in BRENDA P52042 and metacyc::MONOMER-13470 and metacyc::MONOMER-11937 were given EC 1.3.8.1 (which means electron transfer to etf, but no electron bifurcation expected), but are probably electron bifurcating
• Total: 5 characterized proteins

etfA: butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit

• Curated sequence D2RIQ3: butanoyl-CoA dehydrogenase (NAD+, ferredoxin) (subunit 2/3) (EC 1.3.1.109); short-chain acyl-CoA dehydrogenase (EC 1.3.8.1)
• Curated sequence Q18AQ5: butanoyl-CoA dehydrogenase (NAD+, ferredoxin) (subunit 1/3) (EC 1.3.1.109)
• Total: 2 characterized proteins

etfB: butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit

• Curated sequence D2RIQ2: butanoyl-CoA dehydrogenase (NAD+, ferredoxin) (subunit 3/3) (EC 1.3.1.109)
• Curated sequence Q18AQ6: butanoyl-CoA dehydrogenase (NAD+, ferredoxin) (subunit 2/3) (EC 1.3.1.109)
• Total: 2 characterized proteins

ctfA: butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit

• UniProt sequence P33752: RecName: Full=Butyrate--acetoacetate CoA-transferase subunit A; Short=Coat A; EC=2.8.3.9; AltName: Full=Acetoacetyl-CoA:acetate/butyrate:CoA transferase subunit A;
• Comment: cftAB are described in MetaCyc but are absent from the list of curated proteins in this version of GapMind
• Total: 1 characterized proteins

ctfB: butanoyl-CoA:acetoacetate CoA-transferase, beta subunit

• UniProt sequence P23673: RecName: Full=Butyrate--acetoacetate CoA-transferase subunit B; Short=Coat B; EC=2.8.3.9; AltName: Full=Acetoacetyl-CoA:acetate/butyrate CoA-transferase subunit B;
• Total: 1 characterized proteins