Definition of L-lactate catabolism
As rules and steps, or see full text
Rules
Overview: L-lactate degradation in GapMind is based on L-lactate dehydrogenases or oxidases.
- all: L-lactate-transport and L-lactate-degradation
- 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.
- L-lactate-transport:
- lctP
- or SfMCT
- or larD
- or mctP
- or Shew_2731 and Shew_2732
- Comment: Transporters were identified using query: transporter:L-lactate:(S)-lactate:D,L-lactic and prokaryotic lactate transporters were examined as well. Exchangers for lactate/citrate or lactate/malate were ignored.
Steps
lctP: L-lactate:H+ symporter LctP or LidP
- Curated sequence P33231: L-lactate permease. Lactate permease, LctP or LidP (substrates: L-lactate, D-lactate and glycolate). lactate/glycolate:H+ symporter LldP. lactate/glycolate:H+ symporter LldP. (R)-lactate / (S)-lactate / glycolate:H+ symporter LldP
- Curated sequence P71067: L-lactate permease. L-lactate permease
- Curated sequence AO356_07550: L-lactate and D-lactate permease (lctP family)
- Curated sequence Q46839: Glycolate permease, GlcA or YghK (substrates: L-lactate, D-lactate and glycolate). glycolate/lactate:H+ symporter GlcA. glycolate/lactate:H+ symporter GlcA
- Ignore hits to GFF4712 when looking for 'other' hits (D-lactate transporter (lctP family))
- UniProt sequence Q8EGS2: RecName: Full=L-lactate permease {ECO:0000256|RuleBase:RU365092};
- UniProt sequence L0GFN1: RecName: Full=L-lactate permease {ECO:0000256|RuleBase:RU365092};
- Curated sequence P71067: L-lactate permease. L-lactate permease
- Comment: E. coli GlcA (Q46839) is similar to LctP and is reported to transport both L- and D-lactate. PS417_24105 (GFF4172) is important only for D-lactate utilization but is closely related to AO356_07550 and could be an L-lactate transporter as well. SO_1522 (Q8EGS2) and Psest_0955 (L0GFN1) probably transport both isomers. Bacillus subtilis LutP (P71067) is an L-lactate transporter.
- Total: 6 characterized proteins
SfMCT: L-lactate transporter SfMCT
larD: D,L-lactic acid transporter LarD
- Curated sequence F9UST3: D/L-lactic acid transporter; Lactate racemization operon protein LarD; Lactic acid channel. GlpF1; transports water, dihydroxyacetone and glycerol as well as D,L-lactic acid
- Curated sequence F9UMX3: Glycerol uptake facilitator protein 4; D/L-lactic acid transporter; Lactic acid channel
- Total: 2 characterized proteins
mctP: D,L-lactic acid transporter MctP
- Curated sequence Q8VM88: The monocarboxylate uptake (H+ symport?) permease, MctP (transports lactate (Km = 4.4 μM), pyruvate (Km = 3.8), propionate, butyrate (butanoic acid), α-hydroxybutyrate, L- and D-alanine (Km = 0.5 mM), and possibly cysteine and histidine)
- Curated sequence Q1M7A2: Monocarboxylate transport permease protein
- Total: 2 characterized proteins
Shew_2731: L-lactate:Na+ symporter, large component
- Curated sequence 5209923: actP-like component of L-lactate and L-malate uptake system
- Ignore hits to 6937353 when looking for 'other' hits (actP-like component of lactate uptake system)
- Comment: 2-component L-lactate transporter from Shewanella loihica PV-4. A related system in Shewanella amazonesnsis SB2B is also probably a L-lactate transporter (SB2B cannot utilize D-lactate), but its specificity is not proven, so it is marked ignore.
- Total: 1 characterized proteins
Shew_2732: L-lactate:Na+ symporter, small component
- Curated sequence 5209924: small component of L-lactate and L-malate uptake system
- Ignore hits to 6937352 when looking for 'other' hits (small component of lactate uptake system)
- Total: 1 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
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
acs: acetyl-CoA synthetase, AMP-forming
ackA: acetate kinase
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
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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:
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