Definition of L-malate catabolism
As rules and steps, or see full text
Rules
Overview: Since L-malate is a TCA cycle intermediate, catabolic reactions are not represented in GapMind.
- all: L-malate-transport
- L-malate-transport:
- sdlC
- or dctA
- or maeN
- or dctM, dctP and dctQ
- or Dshi_1194 and Dshi_1195
- or mae1
- or mleP
- Comment: Transporters were identified using query: transporter:malate:L-malate:(S)-malate. (None of these transporters seem to be specific for D-malate, although E. coli can grow with D-malate as the sole source of carbon.) In B. subtilis, mleN (P54571) can contribute to growth on malate by a malate:lactate antiport mechanism (PMID:10903309), but it is not clear how this could be the sole malate uptake system for growth (no fixed carbon would be available for growth), so it was excluded.
Steps
sdlC: L-malate:Na+ symporter SdlC
- Curated sequence A4QAL6: The aerobic dicarboxylate (succinate (Km, 30 μM), fumarate (Km, 79
- Curated sequence CH_091173: tonoplast dicarboxylate transporter. Tonoplast dicarboxylate transporter; AttDT; Sodium-dicarboxylate cotransporter-like; AtSDAT; Vacuolar malate transporter. The tonoplast dicarboxylate (malate) transporter, AtDCT
- Curated sequence Q21339: Sodium-dependent high-affinity dicarboxylate transporter 3; Na(+)/dicarboxylate cotransporter 3; NaDC-3; ceNaDC3. High affinity dicarboxylate:Na+ symporter, NaDC2 (INDY2) (relative affinities: fumarate > malate > α-ketoglutarate > maleate > succinate > lactate)
- Curated sequence Q2FFH9: The Na+ (or Li+):dicarboxylate (2:1) symporter, SdcS (catalyzes succinate:succinate antiport as well as electroneutral symport in reconstituted proteoliposomes
- Curated sequence Q65NC0: The Na+-coupled dicarboxylate (succinate; malate; fumarate) transporter, SdcL (transports aspartate, α-ketoglutarate and oxaloacetate with low affinity). Km for succinate, ~6
- Curated sequence Q9KNE0: Dicarboxylate (succinate, fumarate, malate) transporter, vcINDY
- Curated sequence Q99SX1: Sodium-dependent dicarboxylate transporter SdcS; Na(+)/dicarboxylate symporter
- Total: 7 characterized proteins
dctA: L-malate:H+ symporter DctA
- Curated sequence P96603: The dicarboxylate (succinate, fumarate, malate and oxaloacetate):H+ symporter, DctA (probably 3H+ are transported per succinate taken up
- Curated sequence Q01857: C4-dicarboxylate transporter (substrates: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate, mesaconate)
- Curated sequence Q1J1H5: Fumarate:H+ symporter of 442 aas and 14 established TMSs, DctA. Responsible for the transport of dicarboxylates such as succinate, fumarate, and malate
- Curated sequence Q848I3: Organic acid uptake porter, DctA of 444 aas and 8 - 10 putative TMSs
- Curated sequence AO356_18980: sodium:C4-dicarboxylate symporter (dctA)
- Curated sequence Q9I4F5: C4-dicarboxylate transport protein 2
- Curated sequence CH_014038: aerobic C4-dicarboxylate transport protein. Aerobic C4-dicarboxylate transport protein. Aerobic dicarboxylate transporter, DctA. Interacts with the DcuS sensor kinase. C4 dicarboxylate/orotate:H+ symporter. C4 dicarboxylate/orotate:H+ symporter
- Total: 7 characterized proteins
maeN: malate transporter maeN
- Curated sequence O05256: Na(+)-malate symporter; Sodium-dependent malate transporter. Malate:Na+ symporter
- Curated sequence O07032: Malate:lactate antiporter (substrates include: S-lactate, R-lactate, S-malate and S-citramalate)
- Curated sequence P94363: L-malate/citrate:H+ symporter (electroneutral)
- Curated sequence Q53787: L-Malate permease
- Comment: This cluster seems to include both H+ and Na+ dependent malate transporters, as well as Lactococcus lactis mleP or maeP (O07032) which also exports lactate.
- Total: 4 characterized proteins
dctM: L-malate TRAP transporter, large permease component DctM
- Curated sequence O07838: C4-dicarboxylate TRAP transporter large permease protein DctM. DctM, component of Tripartite dicarboxylate:H+ symporter (substrates include: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate and mesaconate)
- Curated sequence 5208943: dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), large permease component
- Curated sequence Q9HU16: C4-dicarboxylate TRAP transporter large permease protein DctM
- UniProt sequence I7DRS6: SubName: Full=TRAP transporter, subunit DctM {ECO:0000313|EMBL:AFO91751.1};
- Ignore hits to 6938090 when looking for 'other' hits (alpha-ketoglutarate TRAP transporter, large permease component)
- Comment: 3-component TRAP transporter dctMPQ. In Phaeobacter inhibens, the system is important for L-malate utilization: PGA1_c20660 = dctM = I7DRS6; PGA1_c20680 = dctP = I7END8; PGA1_c20670 = dctQ = I7EY26. A very similar system is present in Shewanella amazonensis SB2B, which cannot grow on L-malate; it is still possible that this system transports L-malate, so it is marked ignore.
- Total: 4 characterized proteins
dctP: L-malate TRAP transporter, substrate-binding component DctP
- Curated sequence A3QCW5: C4-dicarboxylate-binding periplasmic protein DctP. dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), solute receptor component
- Curated sequence P37735: C4-dicarboxylate-binding periplasmic protein DctP. DctP, component of Tripartite dicarboxylate:H+ symporter (substrates include: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate and mesaconate)
- Curated sequence Q9KQR9: C4-dicarboxylate-binding periplasmic protein DctP
- Curated sequence Q9HU18: C4-dicarboxylate-binding periplasmic protein DctP
- UniProt sequence I7END8: SubName: Full=C4-dicarboxylate-binding periplasmic protein DctP {ECO:0000313|EMBL:AFO91753.1};
- Ignore hits to 6938088 when looking for 'other' hits (alpha-ketoglutarate TRAP transporter, solute receptor component)
- UniProt sequence Q9HVH5: SubName: Full=Probable c4-dicarboxylate-binding protein {ECO:0000313|EMBL:AAG08004.1};
- Curated sequence 5208945: C4-dicarboxylate-binding periplasmic protein DctP. dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), solute receptor component
- Comment: Q9HVH5 = PA4616 is a malate-binding substrate-binding protein (PMC4310620)
- Total: 6 characterized proteins
dctQ: L-malate TRAP tranpsorter, small permease component DctQ
- Curated sequence O07837: C4-dicarboxylate TRAP transporter small permease protein DctQ. DctQ, component of Tripartite dicarboxylate:H+ symporter (substrates include: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate and mesaconate)
- Curated sequence 5208944: dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), small permease component
- UniProt sequence I7EY26: SubName: Full=TRAP transporter, subunit DctQ {ECO:0000313|EMBL:AFO91752.1};
- Ignore hits to 6938089 when looking for 'other' hits (alpha-ketoglutarate TRAP transporter, small permease component)
- Total: 3 characterized proteins
Dshi_1194: TRAP transporter for succinate, fumarate, L-malate, and 2-oxoglutarate, fused 4TM/12TM components
- UniProt sequence A8LI82: SubName: Full=TRAP transporter {ECO:0000313|EMBL:ABV92936.1};
- UniProt sequence E4PQE4: SubName: Full=TRAP transporter, 4TM/12TM fusion protein {ECO:0000313|EMBL:ADP96487.1};
- Comment: The TRAP system Dshi_1194:Dshi_1195 (A8LI82,A8LI83) is important for utilization of succinate, fumarate, L-malate, and 2-oxoglutarate, as is the related system HP15_723:HP15_722 (E4PQE4,E4PQE3).
- Total: 2 characterized proteins
Dshi_1195: TRAP transporter for succinate, fumarate, L-malate, and 2-oxoglutarate, substrate-binding component
- UniProt sequence A8LI83: SubName: Full=TRAP transporter solute receptor {ECO:0000313|EMBL:ABV92937.1};
- UniProt sequence E4PQE3: SubName: Full=Immunogenic protein {ECO:0000313|EMBL:ADP96486.1};
- Total: 2 characterized proteins
mae1: L-malate:H+ symporter Mae1
mleP: malate permease MleP
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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