As text, or see rules and steps
# Lysine degradation in GapMind is based on many metacyc pathways # (metacyc:PWY-5327), including # L-lysine degradation I via cadaverine (metacyc:PWY0-461), # pathway IV via lysine monooxygenase (metacyc:PWY-5280), # pathway V via D-lysine (metacyc:PWY-5283), # pathway VI via lysine 6-aminotransferase (metacyc:PWY-5298), # pathway VIII via lysine 6-dehydrogenase (metacyc:PWY-5314), # and fermentation to acetate and butanoate (metacyc:P163-PWY). # Pathway X (metacyc:PWY-6328) 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. lysP L-lysine:H+ symporter LysP curated:CharProtDB::CH_003129 curated:CharProtDB::CH_091040 curated:CharProtDB::CH_091257 curated:CharProtDB::CH_091412 curated:SwissProt::A0A1D8PPG4 curated:SwissProt::A0A1D8PPI5 curated:SwissProt::A2RNZ6 curated:SwissProt::Q59WU0 curated:TCDB::K7VV21 curated:TCDB::P43059 # Transporters were identified using # query: transporter:lysine:L-lysine:lys:L-lys lysine-transport: lysP LHT L-lysine transporter curated:SwissProt::Q9FKS8 curated:SwissProt::Q9LRB5 curated:SwissProt::Q9SX98 curated:TCDB::Q84WE9 lysine-transport: LHT Slc7a1 L-lysine transporter Slc7a1 curated:CharProtDB::CH_091036 curated:CharProtDB::CH_091271 curated:CharProtDB::CH_091324 lysine-transport: Slc7a1 lysL L-lysine transporter LysL curated:CharProtDB::CH_019644 lysine-transport: lysL # 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). argT L-lysine ABC transporter, substrate-binding component ArgT curated:CharProtDB::CH_003045 curated:TCDB::P09551 curated:TCDB::Q9HU31 curated:reanno::pseudo5_N2C3_1:AO356_05495 curated:reanno::pseudo5_N2C3_1:AO356_09900 curated:reanno::pseudo6_N2E2:Pf6N2E2_2958 uniprot:Q92PA9 uniprot:Q88GX4 hisM L-lysine ABC transporter, permease component 1 (HisM) curated:SwissProt::P0A2I7 curated:SwissProt::P0AEU3 curated:TCDB::Q9HU29 curated:reanno::pseudo5_N2C3_1:AO356_05505 curated:reanno::pseudo5_N2C3_1:AO356_09910 curated:reanno::pseudo6_N2E2:Pf6N2E2_2960 uniprot:Q88GX2 hisQ L-lysine ABC transporter, permease component 2 (HisQ) curated:SwissProt::P0A2I9 curated:SwissProt::P52094 curated:TCDB::Q9HU30 curated:reanno::pseudo5_N2C3_1:AO356_05500 curated:reanno::pseudo5_N2C3_1:AO356_09905 curated:reanno::pseudo6_N2E2:Pf6N2E2_2959 uniprot:Q88GX3 hisP L-lysine ABC transporter, ATPase component HisP curated:CharProtDB::CH_003210 curated:SwissProt::P02915 curated:TCDB::P73721 curated:TCDB::Q9HU32 curated:reanno::pseudo5_N2C3_1:AO356_05515 curated:reanno::pseudo5_N2C3_1:AO356_09895 curated:reanno::pseudo6_N2E2:Pf6N2E2_2962 uniprot:Q88GX0 lysine-transport: argT hisM hisQ hisP # 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. bgtB L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB) curated:TCDB::P73544 curated:TCDB::Q8YSA2 lysine-transport: bgtB hisP # Lysine exporters (LysE), porins, lysine:cadaverine antiporters # (cadB), vacuolar transporters, lysosomal transporters, mitochondrial # carrier proteins, and the schistosome amino acid transporter (TC # 2.A.3.8.3) were excluded. import leucine.steps:atoB # acetyl-CoA acetyltransferase is part of glutaryl-CoA degradation import phenylacetate.steps:glutaryl-CoA-degradation glaH glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD) EC:1.14.11.64 # 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. lhgD L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO) EC:1.1.5.13 curated:metacyc::G1G01-3089-MONOMER EC:1.1.99.2 # Glutarate is an intermediate in L-lysine degradation. As part of # MetaCyc pathway L-lysine degradation I (metacyc:PWY0-461), 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. glutarate-degradation: glaH lhgD gcdG succinyl-CoA:glutarate CoA-transferase EC:2.8.3.13 # Alternatively, as part of pathway IV (metacyc:PWY-5280), # glutarate can be activated to glutaryl-CoA by a # CoA-transferase. Glutaryl-CoA degradation (metacyc:PWY-5177) # 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. glutarate-degradation: gcdG glutaryl-CoA-degradation # Ignore some very-similar 4-aminobutyrate transaminases davT 5-aminovalerate aminotransferase EC:2.6.1.48 ignore:metacyc::MONOMER-11537 ignore:BRENDA::Q0K2K2 # Ignore some very-similar succinate-semialdehyde dehydrogenases davD glutarate semialdehyde dehydrogenase EC:1.2.1.20 ignore:reanno::pseudo3_N2E3:AO353_11505 ignore:metacyc::MONOMER-15736 curated:SwissProt::Q9I6M5 ignore:BRENDA::P25526 ignore:metacyc::MONOMER-20455 ignore:reanno::MR1:200453 # 5-aminovalerate is an intermediate in L-lysine degradation (metacyc:PWY0-461, metacyc:PWY-5280). # 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.) 5-aminovalerate-degradation: davT davD glutarate-degradation # Q06191 is very similar to SMc04386 (P58350), which is specifically important for lysine # utilization. lysN 2-aminoadipate transaminase EC:2.6.1.39 ignore:SwissProt::Q06191 # PP_5260 was shown to be form D-2-hydroxyglutarate (URL:https://doi.org/10.1101/450254). # 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. hglS D-2-hydroxyglutarate synthase curated:reanno::Putida:PP_5260 curated:reanno::pseudo5_N2C3_1:AO356_01105 curated:reanno::Smeli:SMc04383 curated:ecocyc::G6738-MONOMER # 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. ydiJ (R)-2-hydroxyglutarate dehydrogenase EC:1.1.99.39 EC:1.1.99.40 curated:reanno::Putida:PP_4493 uniprot:Q92L08 # L-2-aminoadipate is an intermediate in L-lysine degradation # pathways V and VI (metacyc:PWY-5283, metacyc:PWY-5298). # 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. L-2-aminoadipate-degradation: lysN hglS ydiJ # A0A0H3H393 is very similar to E. coli diaminopimelate decarboxylase # and could not access the paper about it, so do not trust it. cadA lysine decarboxylase EC:4.1.1.18 ignore:BRENDA::A0A0H3H393 # 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). patA cadaverine aminotransferase curated:metacyc::G7596-MONOMER # 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. patD 5-aminopentanal dehydrogenase curated:SwissProt::P77674 ignore_other:1.2.1.19 # 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. all: lysine-transport cadA patA patD 5-aminovalerate-degradation davB L-lysine 2-monooxygenase EC:1.13.12.2 davA 5-aminovaleramidase EC:3.5.1.30 # In pathway IV, the monooxygenase/decarboxylase davB forms # 5-aminopentanamide, which is hydrolyzed to 5-aminovalerate # (5-aminopentanoate). all: lysine-transport davB davA 5-aminovalerate-degradation # Some lysine racemases are very similar to broad-specificity amino # acid racemases (EC 5.1.1.10) alr lysine racemase EC:5.1.1.5 ignore_other:5.1.1.10 # The ribosomal protein P80340 is misannotated in BRENDA amaD D-lysine oxidase EC:1.4.3.3 ignore:BRENDA::P80340 dpkA 1-piperideine-2-carboxylate reductase EC:1.5.1.1 EC:1.5.1.21 amaA L-pipecolate oxidase EC:1.5.3.7 # 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. amaB L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd) EC:1.2.1.31 ignore:BRENDA::Q4L235 ignore_hmm:TIGR03443 ignore:SwissProt::P83402 ignore:SwissProt::P84463 curated:metacyc::MONOMER-12387 uniprot:Q88CC3 uniprot:Q92L07 # 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. all: lysine-transport alr amaD dpkA amaA amaB L-2-aminoadipate-degradation lat L-lysine 6-aminotransferase EC:2.6.1.36 # 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 all: lysine-transport lat amaB L-2-aminoadipate-degradation lysDH L-lysine 6-dehydrogenase EC:1.4.1.18 # 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. all: lysine-transport lysDH amaB L-2-aminoadipate-degradation kamA L-lysine 2,3-aminomutase EC:5.4.3.2 kamD L-beta-lysine 5,6-aminomutase, alpha subunit curated:BRENDA::Q8RHX7 curated:SwissProt::E3PRJ5 kamE L-beta-lysine 5,6-aminomutase, beta subunit curated:BRENDA::Q8RHX8 curated:SwissProt::E3PRJ4 kdd 3,5-diaminohexanoate dehydrogenase EC:1.4.1.11 kce (S)-5-amino-3-oxohexanoate cleavage enzyme EC:2.3.1.247 kal 3-aminobutyryl-CoA deaminase EC:4.3.1.14 # 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 bcd butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit curated:BRENDA::D2RL84 curated:BRENDA::Q18AQ1 ignore:BRENDA::D9TQ00 curated:SwissProt::P52042 curated:metacyc::MONOMER-11937 curated:metacyc::MONOMER-13470 etfA butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit curated:BRENDA::D2RIQ3 curated:BRENDA::Q18AQ5 etfB butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit curated:BRENDA::D2RIQ2 curated:BRENDA::Q18AQ6 # cftAB are described in MetaCyc but are absent from the list of curated proteins # in this version of GapMind ctfA butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit uniprot:P33752 ctfB butanoyl-CoA:acetoacetate CoA-transferase, beta subunit uniprot:P23673 # 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. all: lysine-transport kamA kamD kamE kdd kce kal bcd etfA etfB ctfA ctfB atoB
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:
Otherwise, a candidate is "medium confidence" if either:
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:
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:
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