Definition of L-malate catabolism

GapMind for catabolism of small carbon sources

Definition of L-malate catabolism

# Since L-malate is a TCA cycle intermediate, catabolic reactions are not represented in GapMind.

sdlC	L-malate:Na+ symporter SdlC	curated:TCDB::A4QAL6	curated:CharProtDB::CH_091173	curated:SwissProt::Q21339	curated:TCDB::Q2FFH9	curated:TCDB::Q65NC0	curated:TCDB::Q9KNE0	curated:SwissProt::Q99SX1

# 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 (uniprot: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.
L-malate-transport: sdlC

dctA	L-malate:H+ symporter DctA	curated:TCDB::P96603	curated:TCDB::Q01857	curated:TCDB::Q1J1H5	curated:TCDB::Q848I3	curated:reanno::pseudo5_N2C3_1:AO356_18980	curated:SwissProt::Q9I4F5	curated:CharProtDB::CH_014038
L-malate-transport: dctA

# 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.
maeN	malate transporter maeN	curated:SwissProt::O05256	curated:TCDB::O07032	curated:TCDB::P94363	curated:TCDB::Q53787
L-malate-transport: maeN

# 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.
dctM	L-malate TRAP transporter, large permease component DctM	curated:SwissProt::O07838	curated:reanno::PV4:5208943	curated:SwissProt::Q9HU16	uniprot:I7DRS6	ignore:reanno::SB2B:6938090

# Q9HVH5  = PA4616 is a malate-binding substrate-binding protein (PMC4310620)
dctP	L-malate TRAP transporter, substrate-binding component DctP	curated:SwissProt::A3QCW5	curated:SwissProt::P37735	curated:SwissProt::Q9KQR9	curated:SwissProt::Q9HU18	uniprot:I7END8	ignore:reanno::SB2B:6938088	uniprot:Q9HVH5	curated:reanno::PV4:5208945

dctQ	L-malate TRAP tranpsorter, small permease component DctQ	curated:SwissProt::O07837	curated:reanno::PV4:5208944	uniprot:I7EY26	ignore:reanno::SB2B:6938089

L-malate-transport: dctM dctP dctQ

import succinate.steps:Dshi_1194 Dshi_1195 # TRAP dicarboxylate transporter
L-malate-transport: Dshi_1194 Dshi_1195

mae1	L-malate:H+ symporter Mae1	curated:CharProtDB::CH_016604
L-malate-transport: mae1

mleP	malate permease MleP	curated:TCDB::Q48797
L-malate-transport: mleP

# Eukaryotic antiporters or carrier porters were excluded.
# Eukaryotic translocators (DIT1/DIT2) which export glutamate were excluded.
# Aluminum-activated efflux systems were excluded.

all: L-malate-transport

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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

GapMind for catabolism of small carbon sources