Definition of L-threonine catabolism

As rules and steps, or see full text

Rules

Overview: L-threonine degradation in GapMind is based on MetaCyc pathway I via 2-ketobutyrate formate-lyase (link), pathway II via glycine (link), pathway III via methylglyoxal (link), and pathway IV via threonine aldolase (link). Pathway V is not thought to occur in prokaryotes and is not included.

• all:
  • threonine-transport, tdcB, tdcE and propionyl-CoA-degradation
  • or threonine-transport, tdh, kbl and glycine-degradation
  • or threonine-transport, tdh, tynA and methylglyoxal-degradation
  • or threonine-transport, ltaE, acetaldehyde-degradation and glycine-degradation
  • Comment: 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.) 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. In L-threonine degradation III, tdh forms L-2-amino-3-oxobutanoate, and oxidase tynA forms methylglyoxal. In L-threonine degradation IV, aldolase ltaE cleaves threonine to acetaldehyde and glycine.
• L-lactate-degradation:
  • L-LDH
  • or lldE, lldF and lldG
  • or lutA, lutB and lutC
  • or DVU3033 and DVU3032
  • or lctO and acs
  • or lctO, ackA and pta
  • Comment: Various L-lactate dehydrogenases are known, with different numbers of subunits; these all form pyruvate. Or, after L-lactate oxidase (lctO) forms acetate, the acetate is activated to acetyl-CoA.
• methylglyoxal-degradation:
  • gloA, gloB and D-lactate-dehydrogenase
  • or yvgN, aldA and L-lactate-degradation
  • Comment: In methylglyoxal degradation I (link), 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. In methylglyoxal degradation IV (link), yvgN reduces methylglyoxal to (S)-lactaldehyde, aldA oxidizes it to (S)-lactate (also known as L-lactate).
• D-lactate-dehydrogenase:
  • D-LDH
  • or lctB, lctC and lctD
  • or glcD, glcE and glcF
  • Comment: Acetobacterium woodii uses an electron-bifurcating dehydrogenase (lctBCD) for growth on lactate. The Km for D-lactate is far below that for L-lactate (Km of 3.6 mM vs. 112 mM; PMID:24762045), so we consider it to be a D-lactate dehydrogenase. GlcDEF from E. coli (EC 1.1.99.14) is usually described as glycolate dehydrogenase or glycolate oxidase, but it has similar activity on D-lactate (PMID:4557653), and homologs from various Proteobacteria are important for D-lactate utilization. The physiological electron acceptor is not known, so terming GlcDEF an oxidase is questionable.
• glycine-degradation:
  • glycine-reductase and ackA
  • or glycine-reductase and pta
  • or gcvP, gcvT, gcvH and lpd
  • Comment: 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) Or glycine can cleaved to ammonia, CO2, and 5,10-methylene-tetrahydrofolate by the glycine cleavage system, gcvPTH/lpd.
• glycine-reductase: grdA, grdE, grdB, grdD and grdC
• acetaldehyde-degradation:
  • ald-dh-CoA
  • or adh and acs
  • or adh, ackA and pta
  • Comment: Acetaldehyde can be oxidized to acetyl-CoA, or oxidized to acetate and activated to acetyl-CoA by either acetyl-CoA synthetase (acs) or by acetate kinase (ackA) and phosphate acetyltransferase (pta).
• propionyl-CoA-degradation:
  • prpC, prpD, acn and prpB
  • or prpC, acnD, prpF, acn and prpB
  • or propionyl-CoA-carboxylase, epi and methylmalonyl-CoA-mutase
  • or pco, hpcD, dddA and iolA
  • Comment: In 2-methylcitrate cycle I, propionyl-CoA is combined with oxalacetate (by prpC) to give methylcitrate, dehydrated to cis-2-methylaconitate by prpD, hydrated to (2R,3S)-2-methylisocitrate, and a lyase produces pyruvate and succinate. (We consider succinate as a central intermediate, as most organisms can activate it to succinyl-CoA or can oxidize it to fumarate and convert that to oxaloacetate.) In 2-methylcitrate cycle II, a different dehydratase (acnD) and an isomerase (prpF) replace the dehydratase prpD; acnD dehydrates (2S,3S)-2-methylcitrate to 2-methyl-trans-aconitate, and prpF isomerizes it to cis-2-methylaconitate. In propanoyl CoA degradation I, propionyl-CoA carboxylase forms (S)-methylmalonyl-CoA, methylmalonyl-CoA epimerase forms (R)-methylmalonyl-CoA, and methylmalonyl-CoA mutase forms succinyl-CoA, which is a central metabolite. (Note that methylmalonyl-CoA mutase requires adenosylcobamide, a form of vitamin B12, for activity.) In propanoyl-CoA degradation II: propionyl-CoA is oxidized to acrylyl-CoA by pco, hydrated to 3-hydroxypropionyl-CoA, hydrolzed to 3-hydroxypropionate, oxidized to 3-oxopropionate (malonate semialdehyde), and oxidized to acetyl-CoA and CO2.
• methylmalonyl-CoA-mutase:
  • mcmA
  • or mcm-large and mcm-small
  • Comment: methylmalonyl-CoA mutase has a catalytic domain and a B12-binding domain. These are usually found in the same protein, which we call mcmA. In Metallosphaera and Pyrococcus, the B12-binding domain is a separate subunit. In Propionibacterium and Methylorubrum, there is an additional subunit with a catalytic domain only; this may have a protective role (PMID:14734568) and is not described here. There's also a mcm-interacting GTPase (known as MeaB or YgfD) that loads B12 onto mcm and protects it from inactivation (see PMC4631608); this is not described here. Some fused mcm proteins include a MeaB domain as well (i.e., Q8F222, Q8Y2U5).
• propionyl-CoA-carboxylase:
  • pccA and pccB
  • or pccA1, pccA2 and pccB
  • Comment: propionyl-CoA carboxylase is a heteromer, usually with alpha and beta subunits pccAB. Haloferax mediterranei has a third subunit as well (pccX), which is not described here. Acidianus brierleyi has a diverged pccA split into two pieces.
• threonine-transport:
  • braC, braD, braE, braF and braG
  • or tdcC
  • or sstT
  • or serP1
  • or phtA
  • or snatA
  • or RR42_RS28305
  • Comment: Transporters were identified using query: transporter:threonine:L-threonine:thr

Steps

braC: L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)

• Curated sequence P21175: Leucine-, isoleucine-, valine-, threonine-, and alanine-binding protein; LIVAT-BP; Leu/Ile/Val/Thr/Ala-binding protein. Leucine-, isoleucine-, valine-, threonine-, and alanine-binding protein, component of Branched chain amino acid uptake transporter. Transports alanine
• Curated sequence Q55387: NatB aka SLR0559, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
• Curated sequence Q8YVY4: NatB, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
• Comment: braC and natB are quite distantly related and were not clustered, but both are SBP
• Total: 3 characterized proteins

braD: L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)

• Curated sequence P21627: High-affinity branched-chain amino acid transport system permease protein BraD, component of Branched chain amino acid uptake transporter. Transports alanine
• Curated sequence P74318: NatD aka LivH aka SLR0949, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
• Curated sequence Q8YXD0: NatD, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
• Total: 3 characterized proteins

braE: L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)

• Curated sequence P21628: High-affinity branched-chain amino acid transport system permease protein BraE, component of Branched chain amino acid uptake transporter. Transports alanine
• Curated sequence P74455: NatC aka SLL0146, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
• Curated sequence Q8YY08: NatC, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
• Total: 3 characterized proteins

braF: L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)

• Curated sequence P21629: High-affinity branched-chain amino acid transport ATP-binding protein BraF, component of Branched chain amino acid uptake transporter. Transports alanine
• Curated sequence Q55164: NatA aka BRAF aka SLR0467, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
• Curated sequence Q7A2H0: NatA, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
• Total: 3 characterized proteins

braG: L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)

• Curated sequence P21630: High-affinity branched-chain amino acid transport ATP-binding protein BraG, component of Branched chain amino acid uptake transporter. Transports alanine
• Curated sequence P73650: NatE aka LivF aka SLR1881, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
• Curated sequence Q8YT15: NatE, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
• Total: 3 characterized proteins

tdcC: L-threonine:H+ symporter TdcC

• Curated sequence P0AAD8: Threonine/serine transporter TdcC; H(+)/threonine-serine symporter. Threonine/Serine permease. threonine/serine:H⁺ symporter. threonine/serine:H⁺ symporter
• Total: 1 characterized proteins

sstT: L-threonine:Na+ symporter SstT

• Curated sequence P0AGE4: Serine/threonine transporter SstT; Na(+)/serine-threonine symporter. Serine/threonine:Na+ symporter, SstT. serine/threonine:Na⁺ symporter
• Total: 1 characterized proteins

serP1: L-threonine uptake transporter SerP1

• Curated sequence F2HQ25: Serine uptake transporter, SerP1, of 259 aas and 12 TMSs (Trip et al. 2013). L-serine is the highest affinity substrate (Km = 18 μM), but SerP1 also transports L-threonine and L-cysteine (Km values = 20 - 40 μM)
• Ignore hits to A2RI87 when looking for 'other' hits (Serine permease SerP1)
• Comment: A closely related protein (A2RI87) is annotated as a serine permease only
• Total: 1 characterized proteins

phtA: L-threonine uptake permease PhtA

• Curated sequence Q5ZY33: The threonine uptake permease, PhtA (Sauer et al., 2005) (required for maximal growth in macrophages and Acanthamoeba castellanii)
• Total: 1 characterized proteins

snatA: L-threonine transporter snatA

• Curated sequence Q8J305: The SnatA carrier. Transports glycine, L-alanine, L-serine, L-threonine and a variety of neutral L-amino acids
• Total: 1 characterized proteins

RR42_RS28305: L-threonine:H+ symporter

• UniProt sequence A0A0C4YRF7: SubName: Full=D-serine/D-alanine/glycine transporter {ECO:0000313|EMBL:AJG23156.1};
• Comment: 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)
• Total: 1 characterized proteins

pccA: propionyl-CoA carboxylase, alpha subunit

• Curated sequence P05165: propionyl-CoA carboxylase (subunit 1/2) (EC 6.4.1.3). Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3. propionyl-CoA carboxylase α chain, mitochondrial (EC 6.4.1.3)
• Curated sequence Q19842: propionyl-CoA carboxylase (subunit 2/2) (EC 6.4.1.3). Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3
• Curated sequence I3R7G3: Propionyl-CoA carboxylase, biotin carboxylase and biotin-carboxyl carrier subunit; PCC; EC 6.4.1.3; EC 6.3.4.14. propionyl-CoA carboxylase (subunit 3/3) (EC 6.4.1.3)
• Curated sequence P0DTA4: Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3
• Curated sequence Q5LUF3: Propionyl-CoA carboxylase alpha chain; EC 6.4.1.3. propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence Q91ZA3: Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3
• Curated sequence MONOMER-13589: propionyl-CoA carboxylase α subunit (EC 6.4.1.3)
• Curated sequence MONOMER-8606: propionyl-CoA carboxylase α subunit (EC 6.4.1.3)
• Curated sequence 3607308: Propionyl-CoA carboxylase biotin-containing subunit (EC 6.4.1.3)
• Curated sequence Dsui_0516: Propionyl-CoA carboxylase biotin-containing subunit (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 10 characterized proteins

pccB: propionyl-CoA carboxylase, beta subunit

• Curated sequence P05166: propionyl-CoA carboxylase (subunit 2/2) (EC 6.4.1.3). Propionyl-CoA carboxylase beta chain, mitochondrial; PCCase subunit beta; Propanoyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.3. propionyl-CoA carboxylase β chain, mitochondrial (EC 6.4.1.3)
• Curated sequence Q20676: propionyl-CoA carboxylase (subunit 1/2) (EC 6.4.1.3)
• Curated sequence Q9X4K7: propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence I3R7F1: Propionyl-CoA carboxylase, carboxyltransferase subunit; PCC; EC 6.4.1.3. propionyl-CoA carboxylase (subunit 2/3) (EC 6.4.1.3)
• Curated sequence P53003: Propionyl-CoA carboxylase beta chain; PCCase; Propanoyl-CoA:carbon dioxide ligase; EC 6.4.1.3
• Curated sequence P79384: Propionyl-CoA carboxylase beta chain, mitochondrial; PCCase subunit beta; Propanoyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.3
• Curated sequence Q168G2: Propionyl-CoA carboxylase beta chain; EC 6.4.1.3
• Curated sequence Q3J4E3: Propionyl-CoA carboxylase beta chain; PCCase; Propanoyl-CoA:carbon dioxide ligase; EC 6.4.1.3. propionyl-CoA carboxylase β subunit (EC 6.4.1.3)
• Curated sequence Q99MN9: Propionyl-CoA carboxylase beta chain, mitochondrial; PCCase subunit beta; Propanoyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.3. propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence MONOMER-13598: acyl CoA carboxylase carboxyltransferase subunit (EC 2.1.3.15; EC 6.4.1.3; EC 6.3.4.14). acetyl-CoA carboxylase (subunit 1/3) (EC 6.4.1.2); propionyl-CoA carboxylase (subunit 2/3) (EC 6.4.1.3)
• Curated sequence MONOMER-16260: propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence MONOMER-17283: propionyl-CoA carboxylase α subunit (EC 6.4.1.3)
• Curated sequence MONOMER-17284: propionyl-CoA carboxylase β subunit (EC 6.4.1.3)
• Curated sequence MONOMER-8607: propionyl-CoA carboxylase β subunit (EC 6.4.1.3)
• Curated sequence 3607303: Propionyl-CoA carboxylase carboxyl transferase subunit (EC 6.4.1.3)
• Curated sequence Dsui_0517: Propionyl-CoA carboxylase carboxyl transferase subunit (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 16 characterized proteins

pccA1: propionyl-CoA carboxylase, biotin carboxyl carrier subunit

• Curated sequence MONOMER-13597: acyl CoA carboxylase biotin carboxylase subunit (EC 2.1.3.15; EC 6.4.1.3; EC 6.3.4.14). biotin carboxylase (EC 6.3.4.14); acetyl-CoA carboxylase (subunit 2/3) (EC 6.4.1.2); propionyl-CoA carboxylase (subunit 1/3) (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 1 characterized proteins

pccA2: propionyl-CoA carboxylase, biotin carboxylase subunit

• Curated sequence MONOMER-13596: acyl CoA carboxylase biotin carboxyl carrier protein subunit (EC 2.1.3.15; EC 6.4.1.3; EC 6.3.4.14). acetyl-CoA carboxylase (subunit 3/3) (EC 6.4.1.2); propionyl-CoA carboxylase (subunit 3/3) (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 1 characterized proteins

mcmA: methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components

• Curated sequence O86028: Methylmalonyl-CoA mutase; MCM; EC 5.4.99.2
• Curated sequence P22033: methylmalonyl-CoA mutase (EC 5.4.99.2). Methylmalonyl-CoA mutase, mitochondrial; MCM; Methylmalonyl-CoA isomerase; EC 5.4.99.2. Methylmalonyl-CoA mutase, mitochondrial (EC 5.4.99.2)
• Curated sequence Q23381: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q84FZ1: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q8MI68: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence P27253: Methylmalonyl-CoA mutase; MCM; EC 5.4.99.2. methylmalonyl-CoA mutase (EC 5.4.99.2). methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q3J4D7: Methylmalonyl-CoA mutase; MCM; EC 5.4.99.2. methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence MONOMER-18293: methylmalonyl-CoA mutase subunit (EC 5.4.99.2)
• Curated sequence Dsui_0519: Methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q8F222: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q8Y2U5: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Ignore hits to items matching 5.4.99.2 when looking for 'other' hits
• Total: 11 characterized proteins

mcm-large: methylmalonyl-CoA mutase, large (catalytic) subunit

• Curated sequence A4YEG1: methylmalonyl-CoA mutase (subunit 2/2) (EC 5.4.99.2)
• Curated sequence O74009: methylmalonyl-CoA mutase (subunit 2/2) (EC 5.4.99.2)
• Curated sequence P11653: methylmalonyl-CoA mutase (EC 5.4.99.2). Methylmalonyl-CoA mutase large subunit; MCM-alpha; EC 5.4.99.2. methylmalonyl-CoA mutase large subunit (EC 5.4.99.2)
• Ignore hits to items matching 5.4.99.2 when looking for 'other' hits
• Total: 3 characterized proteins

mcm-small: methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit

• Curated sequence A4YIE3: methylmalonyl-CoA mutase (subunit 1/2) (EC 5.4.99.2)
• Curated sequence O58013: methylmalonyl-CoA mutase (subunit 1/2) (EC 5.4.99.2)
• Ignore hits to items matching 5.4.99.2 when looking for 'other' hits
• Total: 2 characterized proteins

prpC: 2-methylcitrate synthase

• Curated proteins or TIGRFams with EC 2.3.3.5
• Curated sequence P45858: citrate synthase (unknown stereospecificity) (EC 2.3.3.16). Citrate/2-methylcitrate synthase; 2-methylcitrate synthase; 2-MCS; MCS; Citrate synthase; EC 2.3.3.-; EC 2.3.3.16
• Comment: P45858 is annotated by SwissProt as 2-methylcitrate synthase, but without this EC number
• Total: 19 characterized proteins

prpD: 2-methylcitrate dehydratase

• Curated proteins or TIGRFams with EC 4.2.1.79
• Total: 1 HMMs and 11 characterized proteins

acn: (2R,3S)-2-methylcitrate dehydratase

• Curated proteins or TIGRFams with EC 4.2.1.99
• Ignore hits to items matching 4.2.1.3 when looking for 'other' hits
• Comment: (2R,3S)-2-methylcitrate dehydratases are closely related to aconitate hydratases (EC 4.2.1.3), which are ignored.
• Total: 1 HMMs and 10 characterized proteins

prpB: 2-methylisocitrate lyase

• Curated proteins or TIGRFams with EC 4.1.3.30
• Ignore hits to items matching 4.1.3.1 when looking for 'other' hits
• Comment: Many 2-methylisocitrate lyases are closely related to isocitrate lyases (EC 4.1.3.1)
• Total: 1 HMMs and 26 characterized proteins

acnD: 2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)

• Curated proteins or TIGRFams with EC 4.2.1.117
• Ignore hits to Q937N8 when looking for 'other' hits (Aconitate hydratase A; Aconitase; (2R,3S)-2-methylisocitrate dehydratase; (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate dehydratase; Iron-responsive protein-like; IRP-like; Probable 2-methyl-cis-aconitate hydratase; RNA-binding protein; EC 4.2.1.3; EC 4.2.1.99)
• Comment: acnM from Ralstonia eutropha (Q937N8) is proposed to have this activity as well (PMID:11495997), but is annotated in SwissProt as aconitase or (2R,3S)-2-methylisocitrate dehydratase instead
• Total: 1 characterized proteins

prpF: methylaconitate isomerase

• Curated proteins or TIGRFams with EC 5.3.3.7
• Curated sequence Q937N7: 2-methyl-aconitate isomerase; Cis-trans isomerase; EC 5.3.3.-
• Ignore hits to A0A0A1H8I4 when looking for 'other' hits (Aconitate isomerase; AI; EC 5.3.3.7. aconitate DELTA-isomerase (EC 5.3.3.7))
• Comment: SwissProt annotates Q937N7 with this activity, but with a vague EC number. The periplasmic substrate-binding protein A0A0A1H8I4 has aconitate isomerase activity but has a high Km (PMID:26293748), and its periplasmic location would prevent it from participating in the methylcitrate cycle, so it is ignored.
• Total: 3 characterized proteins

epi: methylmalonyl-CoA epimerase

• Curated proteins or TIGRFams with EC 5.1.99.1
• Ignore hits to 3607309 when looking for 'other' hits (Methylmalonyl-CoA epimerase (EC 5.1.99.1))
• Comment: In the fitness browser reannotations, Dshi_0724 from Dinoroseobacter shibae (Dino:3607309) was annotated as the epimerase because it was annotated as such by SEED and it has a specific phenotype on propionate, which seemed to confirm its annotation. But Dshi_0724 belongs to the uncharacterized family DUF4174 / PF13778 and has a signal peptide. Also, D. shibae contains another, apparently essential, epi (Dshi_2630).
• Total: 1 HMMs and 9 characterized proteins

pco: propanyl-CoA oxidase

• Curated proteins or TIGRFams with EC 1.3.3.6
• Total: 27 characterized proteins

hpcD: 3-hydroxypropionyl-CoA dehydratase

• Curated proteins or TIGRFams with EC 4.2.1.116
• Total: 3 characterized proteins

dddA: 3-hydroxypropionate dehydrogenase

• Curated proteins or TIGRFams with EC 1.1.1.59
• Total: 2 characterized proteins

iolA: malonate semialdehyde dehydrogenase (CoA-acylating)

• Curated proteins or TIGRFams with EC 1.2.1.18
• Ignore hits to items matching 1.2.1.27 when looking for 'other' hits
• Ignore hits to Q9I702 when looking for 'other' hits (Putative 3-oxopropanoate dehydrogenase; EC 1.2.1.-)
• Comment: Ignore similarity to methylmalonate semialdehyde dehydrogenase (EC 1.2.1.27), which often has this activity as well
• Total: 11 characterized proteins

ald-dh-CoA: acetaldehyde dehydrogenase, acylating

• Curated proteins or TIGRFams with EC 1.2.1.10
• Ignore hits to items matching 1.1.1.1 when looking for 'other' hits
• Ignore hits to items matching 1.1.1.71 when looking for 'other' hits
• Ignore hits to items matching 1.2.1.57 when looking for 'other' hits
• Ignore hits to Q2XQZ7 when looking for 'other' hits (4-hydroxy-2-oxovalerate aldolase (EC 4.1.3.39))
• Comment: Many enzymes are multifunctional alcohol/acetaldehyde dehydrogenases, and many close homologs have just one annotation. EC 1.2.1.57 is acylating butanal dehydrogenase, which may also act on acetaldehyde. Q2XQZ7 is probably misannotated.
• Total: 2 HMMs and 20 characterized proteins

adh: acetaldehyde dehydrogenase (not acylating)

• Curated proteins or TIGRFams with EC 1.2.1.3
• Total: 70 characterized proteins

acs: acetyl-CoA synthetase, AMP-forming

• Curated proteins or TIGRFams with EC 6.2.1.1
• Total: 1 HMMs and 28 characterized proteins

ackA: acetate kinase

• Curated proteins or TIGRFams with EC 2.7.2.1
• Curated proteins or TIGRFams with EC 2.7.2.15
• Total: 1 HMMs and 25 characterized proteins

pta: phosphate acetyltransferase

• Curated proteins or TIGRFams with EC 2.3.1.8
• Ignore hits to P32796 when looking for 'other' hits (carnitine O-acetyltransferase (EC 2.3.1.7); phosphate acetyltransferase (EC 2.3.1.8). Carnitine O-acetyltransferase, mitochondrial; Carnitine acetylase; EC 2.3.1.7)
• Comment: BRENDA misannotates yeast's carnitine acetyltransferase with EC 2.3.1.8
• Total: 1 HMMs and 18 characterized proteins

grdA: glycine reductase component A1

• Curated sequence P26971: glycine reductase (EC 1.21.4.2)
• Curated sequence Q185M6: glycine reductase (EC 1.21.4.2)
• Curated sequence MONOMER-13142: glycine reductase system component A (EC 1.21.4.2)
• Curated sequence MONOMER-20600: glycine/sarcosine/betaine reductase complex component A1 (EC 1.21.4.2)
• Ignore hits to items matching 1.21.4.2 when looking for 'other' hits
• Total: 4 characterized proteins

grdE: glycine reductase component B, precursor to alpha/beta subunits

• Curated sequence Q9R4G7: glycine reductase, subunits ABC; EC 1.21.4.2. glycine reductase (EC 1.21.4.2)
• Ignore hits to items matching 1.21.4.2 when looking for 'other' hits
• Total: 1 characterized proteins

grdB: glycine reductase component B, gamma subunit

• Curated sequence CH_090869: glycine reductase, selenoprotein B; EC 1.21.4.2
• Ignore hits to items matching 1.21.4.2 when looking for 'other' hits
• Total: 1 characterized proteins

grdD: glycine reductase component C, alpha subunit

• Curated sequence CH_013101: glycine reductase complex component C, alpha subunit; EC 1.21.4.2; EC 1.21.4.3; EC 1.21.4.4
• Ignore hits to items matching 1.21.4.2 when looking for 'other' hits
• Total: 1 characterized proteins

grdC: glycine reductase component C, beta subunit

• Curated sequence CH_017328: glycine reductase complex component C, beta subunit; EC 1.21.4.2; EC 1.21.4.3; EC 1.21.4.4
• Ignore hits to items matching 1.21.4.2 when looking for 'other' hits
• Total: 1 characterized proteins

gcvP: glycine cleavage system, P component (glycine decarboxylase)

• Curated proteins or TIGRFams with EC 1.4.4.2
• Ignore hits to P23434 when looking for 'other' hits (glycine dehydrogenase (aminomethyl-transferring) (EC 1.4.4.2). Glycine cleavage system H protein, mitochondrial; Lipoic acid-containing protein. glycine cleavage system H protein, mitochondrial)
• Ignore hits to P25855 when looking for 'other' hits (glycine dehydrogenase (aminomethyl-transferring) (EC 1.4.4.2). Glycine cleavage system H protein 1, mitochondrial. glycine decarboxylase H protein)
• Comment: Sometimes the H component is given this EC number as well.
• Total: 1 HMMs and 15 characterized proteins

gcvT: glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)

• Curated proteins or TIGRFams with EC 2.1.2.10
• Total: 1 HMMs and 8 characterized proteins

gcvH: glycine cleavage system, H component (lipoyl protein)

• Curated proteins matching Glycine cleavage system H
• Curated proteins matching glycine decarboxylase H
• Total: 16 characterized proteins

lpd: dihydrolipoyl dehydrogenase

• Curated proteins or TIGRFams with EC 1.8.1.4
• Total: 1 HMMs and 45 characterized proteins

gloA: glyoxylase I

• Curated proteins or TIGRFams with EC 4.4.1.5
• Ignore hits to P84719 when looking for 'other' hits (Putative lactoylglutathione lyase; Aldoketomutase; Glyoxalase I; Glx I; Ketone-aldehyde mutase; Methylglyoxalase; PS3; S-D-lactoylglutathione methylglyoxal lyase; EC 4.4.1.5)
• Comment: Ignore the protein fragment P84719
• Total: 1 HMMs and 26 characterized proteins

gloB: hydroxyacylglutathione hydrolase (glyoxalase II)

• Curated proteins or TIGRFams with EC 3.1.2.6
• Total: 1 HMMs and 18 characterized proteins

D-LDH: D-lactate dehydrogenase

• Curated proteins or TIGRFams with EC 1.1.1.28
• Curated proteins or TIGRFams with EC 1.1.99.6
• Curated proteins or TIGRFams with EC 1.1.2.4
• UniProt sequence Q8EGS3: SubName: Full=Respiratory FAD-dependent D-lactate dehydrogenase Dld {ECO:0000313|EMBL:AAN54582.2}; EC=1.1.2.4 {ECO:0000313|EMBL:AAN54582.2};
• Curated sequence Q1GAA2: D-2-hydroxyacid dehydrogenase (NAD+) (EC 1.1.1.345)
• Curated sequence Q48534: D-2-hydroxyacid dehydrogenase (NAD+) (EC 1.1.1.345)
• Comment: PMID:19196979 showed that dld-II (SO_1521, Q8EGS3) is a D-lactate dehydrogenase. D-lactate dehydrogenases from Lactobacillus delbrueckii are annotated as EC 1.1.1.345 (D-2-hydroxyacid dehydrogenase), which is usually used for enzymes that prefer larger substrates.
• Total: 31 characterized proteins

lctB: electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit

• Curated sequence H6LBB0: lactate dehydrogenase (NAD+, ferredoxin) (subunit 3/3) (EC 1.3.1.110)
• Ignore hits to items matching 1.3.1.110 when looking for 'other' hits
• Comment: lctB = Awo_c08710 is the small Etf subunit
• Total: 1 characterized proteins

lctC: electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit

• Curated sequence H6LBB1: lactate dehydrogenase (NAD+, ferredoxin) (subunit 2/3) (EC 1.3.1.110)
• Ignore hits to items matching 1.3.1.110 when looking for 'other' hits
• Comment: lctC = Awo_c08720 is the large Etf subunit
• Total: 1 characterized proteins

lctD: D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component

• Curated sequence H6LBS1: lactate dehydrogenase (NAD+, ferredoxin) (subunit 1/3) (EC 1.3.1.110)
• Ignore hits to items matching 1.3.1.110 when looking for 'other' hits
• Comment: lctD = Awo_c08730 is the LDH subunit
• Total: 1 characterized proteins

glcD: D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)

• Curated sequence RR42_RS17300: D-lactate oxidase, FAD-linked subunit (EC 1.1.3.15)
• Curated sequence GFF2925: D-lactate oxidase, FAD-linked subunit (EC 1.1.3.15)
• Curated sequence SMc00832: D-lactate oxidase, FAD-linked subunit (EC 1.1.3.15)
• Curated sequence GFF3772: D-lactate oxidase and glycolate oxidase, FAD-linked subunit (EC 1.1.3.15)
• Curated sequence P0AEP9: glycolate oxidase subunit glcD. Glycolate oxidase subunit GlcD; Glycolate dehydrogenase subunit GlcD; EC 1.1.99.14. glycolate dehydrogenase, putative FAD-linked subunit (EC 1.1.99.14). glycolate dehydrogenase, putative FAD-linked subunit (EC 1.1.99.14)
• Ignore hits to items matching 1.1.99.14 when looking for 'other' hits
• Total: 5 characterized proteins

glcE: D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)

• Curated sequence RR42_RS17310: D-lactate oxidase, FAD binding subunit (EC 1.1.3.15)
• Curated sequence GFF2924: D-lactate oxidase, FAD binding subunit (EC 1.1.3.15)
• Curated sequence SMc00833: D-lactate oxidase, FAD binding subunit (EC 1.1.3.15)
• Curated sequence GFF3771: D-lactate oxidase and glycolate oxidase, FAD binding subunit (EC 1.1.3.15)
• Curated sequence P52073: Glycolate oxidase subunit GlcE; Glycolate dehydrogenase subunit GlcE; EC 1.1.99.14. glycolate oxidase, subunit glcE. glycolate dehydrogenase, putative FAD-binding subunit (EC 1.1.99.14). glycolate dehydrogenase, putative FAD-binding subunit (EC 1.1.99.14)
• Ignore hits to items matching 1.1.99.14 when looking for 'other' hits
• Total: 5 characterized proteins

glcF: D-lactate dehydrogenase, FeS subunit GlcF

• Curated sequence RR42_RS17315: D-lactate oxidase, iron-sulfur subunit (EC 1.1.3.15)
• Curated sequence GFF2923: D-lactate oxidase, iron-sulfur subunit (EC 1.1.3.15)
• Curated sequence SMc00926: D-lactate oxidase, iron-sulfur subunit (EC 1.1.3.15)
• Curated sequence GFF3770: D-lactate oxidase and glycolate oxidase, iron-sulfur subunit (EC 1.1.3.15)
• Curated sequence P52074: glycolate oxidase, iron-sulfur subunit. Glycolate oxidase iron-sulfur subunit; Glycolate dehydrogenase subunit GlcF; Glycolate oxidase subunit GlcF; EC 1.1.99.14. glycolate dehydrogenase, putative iron-sulfur subunit (EC 1.1.99.14). glycolate dehydrogenase, putative iron-sulfur subunit (EC 1.1.99.14)
• Ignore hits to items matching 1.1.99.14 when looking for 'other' hits
• Total: 5 characterized proteins

yvgN: methylglyoxal reductase (NADPH-dependent)

• Curated proteins or TIGRFams with EC 1.1.1.283
• Ignore hits to items matching 1.1.1.184 when looking for 'other' hits
• Comment: 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.
• Total: 5 characterized proteins

aldA: lactaldehyde dehydrogenase

• Curated proteins or TIGRFams with EC 1.2.1.22
• Ignore hits to items matching lactaldehyde dehydrogenase when looking for 'other' hits
• Comment: The EC number is for the NAD dependent reaction. There's also a NADP dependent reaction, sometimes given this EC, sometimes not.
• Total: 10 characterized proteins

L-LDH: L-lactate dehydrogenase

• Curated proteins or TIGRFams with EC 1.1.2.3
• Curated proteins or TIGRFams with EC 1.1.1.27
• Ignore hits to A0A0H3W5K4 when looking for 'other' hits (acetaldehyde dehydrogenase (acetylating) (EC 1.2.1.10). alcohol dehydrogenase (EC 1.1.1.1); L-lactate dehydrogenase (EC 1.1.1.27); acetaldehyde dehydrogenase (acetylating) (EC 1.2.1.10))
• Ignore hits to I3VSF1 when looking for 'other' hits (acetaldehyde dehydrogenase (acetylating) (EC 1.2.1.10). alcohol dehydrogenase (EC 1.1.1.1); L-lactate dehydrogenase (EC 1.1.1.27); acetaldehyde dehydrogenase (acetylating) (EC 1.2.1.10))
• Comment: A0A0H3W5K4/I3VSF1 appears to be misannotated in BRENDA
• Total: 2 HMMs and 55 characterized proteins

lldE: L-lactate dehydrogenase, LldE subunit

• UniProt sequence Q8EGS4: SubName: Full=L-lactate dehydrogenase complex protein LldE {ECO:0000313|EMBL:AAN54581.1};
• UniProt sequence B2TBW0: SubName: Full=Uncharacterized protein {ECO:0000313|EMBL:ACD19787.1};
• Comment: A three-component L-lactate dehydrogenase LldEFG was described in Shewanella oneidensis (see PMID:19196979). A related system in Burkholderia phytofirmans PsJN is also required for L-lactate utilization; the lldEF subunits are quite similar but the lldG is diverged. LldE = SO_1520 or BPHYT_RS26975
• Total: 2 characterized proteins

lldF: L-lactate dehydrogenase, LldF subunit

• UniProt sequence Q8EGS5: SubName: Full=L-lactate dehydrogenase iron-sulfur cluster-binding protein LldF {ECO:0000313|EMBL:AAN54580.1};
• UniProt sequence B2TBY8: RecName: Full=4Fe-4S ferredoxin-type domain-containing protein {ECO:0000259|PROSITE:PS51379};
• Comment: LldF = SO_1519 or BPHYT_RS26970
• Total: 2 characterized proteins

lldG: L-lactate dehydrogenase, LldG subunit

• UniProt sequence Q8EGS6: SubName: Full=L-lactate dehydrogenase complex protein LldG {ECO:0000313|EMBL:AAN54579.1};
• UniProt sequence B2TBY7: RecName: Full=LUD_dom domain-containing protein {ECO:0000259|Pfam:PF02589};
• Comment: LldG = SO_1518 or BPHYT_RS26965
• Total: 2 characterized proteins

lutA: L-lactate dehydrogenase, LutA subunit

• Curated sequence O07020: Lactate utilization protein A
• Curated sequence Q81GA5: Lactate utilization protein A
• UniProt sequence A0A0C4YIN5: SubName: Full=Putative L-lactate dehydrogenase, Fe-S oxidoreductase subunit YkgE {ECO:0000313|EMBL:AJG21694.1};
• UniProt sequence E4PLR5: SubName: Full=Uncharacterized protein {ECO:0000313|EMBL:ADP99852.1};
• Comment: A three-component L-lactate dehydrogenase LutABC was described in Bacillus subtilis (PMC3347220, PMC2668416). Although LutABC does not seem to have been studied biochemically, it is required for L-lactate utilization, and induced during growth on L-lactate, and is distantly related to lldEFG. The related system from B. cereus has also been studied. Based on fitness data, similar systems were identified in Cupriavidus basilensis FW507-4G11 (lutA = RR42_RS21295; lutB = RR42_RS21285; lutC = RR42_RS21290) and Marinobacter adhaerens HP15 (lutA = HP15_4088, lutB = HP15_4089, lutC = HP15_4090).
• Total: 4 characterized proteins

lutB: L-lactate dehydrogenase, LutB subunit

• Curated sequence O07021: Lactate utilization protein B
• Curated sequence Q81GA4: Lactate utilization protein B
• UniProt sequence A0A0C4Y8G6: SubName: Full=Putative L-lactate dehydrogenase, Iron-sulfur cluster-binding subunit YkgF {ECO:0000313|EMBL:AJG21692.1};
• UniProt sequence E4PLR6: SubName: Full=Iron-sulfur cluster binding protein {ECO:0000313|EMBL:ADP99853.1};
• Total: 4 characterized proteins

lutC: L-lactate dehydrogenase, LutC subunit

• Curated sequence O32259: Lactate utilization protein C
• Curated sequence Q81GA3: Lactate utilization protein C
• UniProt sequence A0A0C4YFN9: RecName: Full=LUD_dom domain-containing protein {ECO:0000259|Pfam:PF02589};
• UniProt sequence E4PLR7: SubName: Full=Protein containing DUF162 {ECO:0000313|EMBL:ADP99854.1};
• Total: 4 characterized proteins

DVU3033: L-lactate dehydrogenase, fused LutA/LutB components

• UniProt sequence Q726S3: SubName: Full=Iron-sulfur cluster-binding protein {ECO:0000313|EMBL:AAS97504.1};
• Comment: In Desulfovibrio vulgaris Hildenborough, a 2-component L-lactate dehydrogenase (DVU3032 and DVU3033) was identified (PMC4481167). Genome-wide fitness data did not identify any additional components. DVU3033 appears to be a fusion of lutA and lutB, and DVU3032 is distantly related to lutC
• Total: 1 characterized proteins

DVU3032: L-lactate dehydrogenase, LutC-like component

• UniProt sequence Q726S4: RecName: Full=LUD_dom domain-containing protein {ECO:0000259|Pfam:PF02589};
• Total: 1 characterized proteins

lctO: L-lactate oxidase or 2-monooxygenase

• Curated proteins or TIGRFams with EC 1.13.12.4
• Curated proteins or TIGRFams with EC 1.1.3.2
• Ignore hits to items matching 1.1.3.15 when looking for 'other' hits
• Comment: L-lactate oxidase (EC 1.13.12.4, formerly 1.1.3.2) oxidizes L-lactate to acetate and CO2 under aerobic conditions. Some of these enzymes produce pyruvate (and hydroxgen peroxide) instead, but are still given this EC number. Either way, the acetate can be used for growth. However this enzyme is mostly found in fermentative bacteria, so its role could be to detoxify the accumulated lactate. Since L-lactate is a (S)-2-hydroxy-acid, ignore any similarities to (S)-2-hydroxy-acid oxidases (1.1.3.15)
• Total: 7 characterized proteins

tdcB: L-threonine dehydratase

• Curated proteins or TIGRFams with EC 4.3.1.19
• Curated sequence CH_124219: threonine deaminase [Arxula adeninivorans]
• Comment: CH_124219 is annotated as this but without the EC number
• Total: 3 HMMs and 18 characterized proteins

tdcE: 2-ketobutyrate formate-lyase

• Curated sequence P42632: pyruvate formate-lyase 4/2-ketobutyrate formate-lyase. PFL-like enzyme TdcE; Keto-acid formate acetyltransferase; Keto-acid formate-lyase; Ketobutyrate formate-lyase; KFL; Pyruvate formate-lyase; PFL; EC 2.3.1.-; EC 2.3.1.54
• Curated sequence P09373: formate C-acetyltransferase (EC 2.3.1.54). pyruvate formate-lyase
• Ignore hits to items matching 2.3.1.54 when looking for 'other' hits
• Comment: 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.
• Total: 2 characterized proteins

tdh: L-threonine 3-dehydrogenase

• Curated proteins or TIGRFams with EC 1.1.1.103
• Total: 1 HMMs and 12 characterized proteins

kbl: glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)

• Curated proteins or TIGRFams with EC 2.3.1.29
• Total: 1 HMMs and 9 characterized proteins

tynA: aminoacetone oxidase

• Curated proteins or TIGRFams with EC 1.4.3.21
• Total: 19 characterized proteins

ltaE: L-threonine aldolase

• Curated proteins or TIGRFams with EC 4.1.2.5
• Curated proteins or TIGRFams with EC 4.1.2.48
• Ignore hits to P0A825 when looking for 'other' hits (glycine hydroxymethyltransferase (EC 2.1.2.1); low-specificity L-threonine aldolase (EC 4.1.2.48). serine hydroxymethyltransferase; EC 2.1.2.1. Serine hydroxymethyltransferase; SHMT; Serine methylase; EC 2.1.2.1. serine hydroxymethyltransferase (EC 2.1.2.1). serine hydroxymethyltransferase (EC 2.1.2.1))
• Ignore hits to D3DKC4 when looking for 'other' hits (Serine hydroxymethyltransferase; SHMT; Serine methylase; L-threonine/L-allo-threonine aldolase; EC 2.1.2.1; EC 4.1.2.48)
• Ignore hits to CH_123166 when looking for 'other' hits (L-threonine aldolase)
• Comment: 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.
• Total: 13 characterized proteins