As text, or see rules and steps
# L-threonine degradation in GapMind is based on MetaCyc # pathway I via 2-ketobutyrate formate-lyase (metacyc:PWY-5437), # pathway II via glycine (metacyc:THREONINE-DEG2-PWY), # pathway III via methylglyoxal (metacyc:THRDLCTCAT-PWY), # and pathway IV via threonine aldolase (metacyc:PWY-5436). # Pathway V is not thought to occur in prokaryotes and is not included. # ABC transporters: BraCDEFG from Pseudomonas aeruginosa and LivJFGHM from Streptococcus pneumoniae. # A related system, NatABCDE from Anabaena PCC 7120 (transporter N-I), is also thought to transport threonine # (see PMC177005; the genes are in TC 3.A.1.4.6). # These are all described by the rules for braCDEFG. import alanine.steps:braC braD braE braF braG # Transporters were identified using # query: transporter:threonine:L-threonine:thr threonine-transport: braC braD braE braF braG tdcC L-threonine:H+ symporter TdcC curated:SwissProt::P0AAD8 threonine-transport: tdcC sstT L-threonine:Na+ symporter SstT curated:SwissProt::P0AGE4 threonine-transport: sstT # A closely related protein (uniprot:A2RI87) is annotated as a serine permease only serP1 L-threonine uptake transporter SerP1 curated:TCDB::F2HQ25 ignore:SwissProt::A2RI87 threonine-transport: serP1 phtA L-threonine uptake permease PhtA curated:TCDB::Q5ZY33 threonine-transport: phtA snatA L-threonine transporter snatA curated:TCDB::Q8J305 threonine-transport: snatA # Specifically important for threonine utilization, and downstream of kbl and tdh. # Homologs are D/L-alanine or serine:H+ symporters # (i.e., E. coli cycA) RR42_RS28305 L-threonine:H+ symporter uniprot:A0A0C4YRF7 threonine-transport: RR42_RS28305 # Serine/threonine exchangers, exporters, and non-specific metazoan transporters were ignored. # propionyl-CoA is a common intermediate in threonine degradation import propionate.steps:propionyl-CoA-degradation # Acetaldehyde is an intermediate in threonine degradation. # Also ackA (acetate kinase) and pta are involved in consuming acetyl phosphate. import ethanol.steps:acetaldehyde-degradation ackA pta # glycine is an intermediate in threonine utilization grdA glycine reductase component A1 curated:BRENDA::P26971 curated:BRENDA::Q185M6 curated:metacyc::MONOMER-13142 curated:metacyc::MONOMER-20600 ignore_other:1.21.4.2 grdE glycine reductase component B, precursor to alpha/beta subunits curated:BRENDA::Q9R4G7 ignore_other:1.21.4.2 grdB glycine reductase component B, gamma subunit curated:CharProtDB::CH_090869 ignore_other:1.21.4.2 grdD glycine reductase component C, alpha subunit curated:CharProtDB::CH_013101 ignore_other:1.21.4.2 grdC glycine reductase component C, beta subunit curated:CharProtDB::CH_017328 ignore_other:1.21.4.2 glycine-reductase: grdA grdE grdB grdD grdC # Glycine can be reduced to acetyl phosphate by glycine reductase (EC:1.21.4.2), and then # converted to acetate (by ackA in reverse) or acetyl-CoA (by pta) glycine-degradation: glycine-reductase ackA glycine-degradation: glycine-reductase pta # Sometimes the H component is given this EC number as well. gcvP glycine cleavage system, P component (glycine decarboxylase) EC:1.4.4.2 ignore:SwissProt::P23434 ignore:SwissProt::P25855 gcvT glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase) EC:2.1.2.10 gcvH glycine cleavage system, H component (lipoyl protein) term:Glycine cleavage system H term:glycine decarboxylase H lpd dihydrolipoyl dehydrogenase EC:1.8.1.4 # Or glycine can cleaved to ammonia, CO2, and 5,10-methylene-tetrahydrofolate # by the glycine cleavage system, gcvPTH/lpd. glycine-degradation: gcvP gcvT gcvH lpd # methylglyoxal is an intermediate in threonine degradation. # Ignore the protein fragment P84719 gloA glyoxylase I EC:4.4.1.5 ignore:SwissProt::P84719 gloB hydroxyacylglutathione hydrolase (glyoxalase II) EC:3.1.2.6 import D-lactate.steps:D-lactate-dehydrogenase # In methylglyoxal degradation I (metacyc:PWY-5386), # gloA condenses methylglyoxal with glutathione to # (R)-S-lactoylglutathione, gloB cleaves it to D-lactate (also known as # (R)-lactate) and glutathione, and the lactate is oxidized to # pyruvate. methylglyoxal-degradation: gloA gloB D-lactate-dehydrogenase # MetaCyc Pathway: methylglyoxal degradation II is not thought to # occur in prokaryotes and is not described here. # MetaCyc Pathway: methylglyoxal degradation III involves reduction to # hydroxyacetone and then to (S)-propane-1,2-diol. This does not lead # to any usable carbon and is not described here. # 1.1.1.184 describes relatively non-specific ketone reductases, some of which are related to # methylglyoxal reductases and may well have that activity as well. yvgN methylglyoxal reductase (NADPH-dependent) EC:1.1.1.283 ignore_other:1.1.1.184 import rhamnose.steps:aldA # lactaldehyde dehydrogenase import L-lactate.steps:L-lactate-degradation # In methylglyoxal degradation IV (metacyc:PWY-5459), yvgN reduces # methylglyoxal to (S)-lactaldehyde, aldA oxidizes it to (S)-lactate (also known as # L-lactate). methylglyoxal-degradation: yvgN aldA L-lactate-degradation # MetaCyc Pathway: methylglyoxal degradation V is very similar to # pathway IV but with a different L-lactate dehydrogenase. # MetaCyc Pathway: methylglyoxal degradation VI # is not thought to occur in prokaryotes and is not described here. # MetaCyc Pathway: methylglyoxal degradation VII involves a # methylglyoxal oxidase that converts it to pyruvate. This pathway is # not thought to occur in prokaryotes and is not described here. # CH_124219 is annotated as this but without the EC number tdcB L-threonine dehydratase EC:4.3.1.19 curated:CharProtDB::CH_124219 # This reaction is not linked to an EC number. # E. coli tdcB (PF42632) and pflB (P09373) seem to be the only ones that are characterized. # Many pyruvate-formate lyases (EC 2.3.1.54) can probably carry out this reaction, so they are ignored. tdcE 2-ketobutyrate formate-lyase curated:SwissProt::P42632 curated:BRENDA::P09373 ignore_other:2.3.1.54 # In L-threonine degradation I, threonine dehydratase (tdcB) # forms 2-iminbutanoate, which is deaminated # to 2-oxobutanoate (either by the same enzyme or by ridA); # then formate-lyase (tdcE) converts this to propanoyl-CoA. # (MetaCyc also includes conversion to propanoate, which forms ATP, but this does not allow for # growth unless the formate can be utilized.) all: threonine-transport tdcB tdcE propionyl-CoA-degradation tdh L-threonine 3-dehydrogenase EC:1.1.1.103 kbl glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase) EC:2.3.1.29 # In L-threonine degradation II, a dehydrogenase (tdh) # forms L-2-amino-3-oxobutanoate, and a C-acetyltransferase (kbl) # cleaves this to acetyl-CoA and glycine. all: threonine-transport tdh kbl glycine-degradation tynA aminoacetone oxidase EC:1.4.3.21 # In L-threonine degradation III, tdh forms L-2-amino-3-oxobutanoate, # and oxidase tynA forms methylglyoxal. all: threonine-transport tdh tynA methylglyoxal-degradation # Some serine hydroxymethyltransferases (glyA) are reported to carry out # the L-threonine aldolase reaction, but the Km are high (see PMC219072 or PMID:22141341). # CharProtDB::CH_123166 is annotated as threonine aldolase but without the EC number, and is nearly identical to # O13427, which is a low-specificity threonine aldolase. ltaE L-threonine aldolase EC:4.1.2.5 EC:4.1.2.48 ignore:SwissProt::P0A825 ignore:SwissProt::D3DKC4 ignore:CharProtDB::CH_123166 # In L-threonine degradation IV, aldolase ltaE # cleaves threonine to acetaldehyde and glycine. all: threonine-transport ltaE acetaldehyde-degradation glycine-degradation
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