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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About GapMind
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 the paper from 2019 on GapMind for amino acid biosynthesis, the paper from 2022 on GapMind for carbon sources, or view the source code.
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