Definition of D-lactate catabolism
As rules and steps, or see full text
Rules
Overview: D-lactate catabolism in GapMind is based on D-lactate dehydrogenases, which form pyruvate.
- all: D-lactate-transport and D-lactate-dehydrogenase
- 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.
- D-lactate-transport:
Steps
lctP: D-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 GFF4712: D-lactate transporter (lctP family)
- 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
- UniProt sequence Q8EGS2: RecName: Full=L-lactate permease {ECO:0000256|RuleBase:RU365092};
- UniProt sequence L0GFN1: RecName: Full=L-lactate permease {ECO:0000256|RuleBase:RU365092};
- Comment: E. coli GlcA (Q46839) is similar to LctP and is reported to transport both L- and D-lactate. SO_1522 (Q8EGS2) and Psest_0955 (L0GFN1) probably transport both isomers. (For evidence that SO_1522 transports D-lactate, see PMID:28285200.)
- Total: 6 characterized proteins
larD: D,L-lactic acid transporter
- 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
- 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
PGA1_c12640: D-lactate ABC transporter, ATP-binding component
PGA1_c12650: D-lactate ABC transporter, permease component 1
PGA1_c12660: D-lactate ABC transporter, permease component 2
PGA1_c12670: D-lactate ABC transporter, substrate-binding component
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
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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