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:
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
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
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)
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
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, ecocyc:G6913-MONOMER) 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
davA: 5-aminovaleramidase
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
amaA: L-pipecolate oxidase
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
lysDH: L-lysine 6-dehydrogenase
kamA: L-lysine 2,3-aminomutase
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
kce: (S)-5-amino-3-oxohexanoate cleavage enzyme
kal: 3-aminobutyryl-CoA deaminase
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
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About GapMind
Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using
ublast (a fast alternative to protein BLAST)
against a database of manually-curated proteins (most of which are experimentally characterized) or by using
HMMer with enzyme models (usually from
TIGRFam). Ublast hits may be split across two different proteins.
A candidate for a step is "high confidence" if either:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
Other blast hits with at least 50% coverage are "low confidence."
Steps with no high- or medium-confidence candidates may be considered "gaps."
For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways.
For diverse bacteria and archaea that can utilize a carbon source, there is a complete
high-confidence catabolic pathway (including a transporter) just 38% of the time, and
there is a complete medium-confidence pathway 63% of the time.
Gaps may be due to:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).
For more information, see the paper from 2019 on GapMind for amino acid biosynthesis, the paper from 2022 on GapMind for carbon sources, or view the source code.
If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know
by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory