Definition of succinate catabolism

GapMind for catabolism of small carbon sources

Definition of succinate catabolism

# GapMind represents succinate uptake only, as succinate is part of
# central metabolism. Specifically, succinate can be consumed by the
# TCA cycle enzymes succinate dehydrogenase, fumarase (forming
# L-malate), and malate dehydrogenase (either decarboxylating, with
# pyruvate as the product, or not, with oxalacetate with the product;
# both compounds are central metabolic intermediates). It's also
# possible that malate could be decarboxylated to lactate, as in
# malolactic fermentation by lactic acid bacteria.

# (Sodium-dependent dicarboxylate transporter SdcS (Q99SX1) was not originally included
#  because the description did not mention succinate specifically.)
sdc	succinate:Na+ symporter Sdc	curated:TCDB::A4QAL6	curated:SwissProt::Q21339	curated:TCDB::Q2FFH9	curated:TCDB::Q65NC0	curated:TCDB::Q9KNE0	curated:SwissProt::Q99SX1

# Transporters were identified using
# query: transporter:succinate
succinate-transport: sdc

# not initially included were AO356_18980, Q9I4F5, or Q01857.
dctA	succinate:H+ symporter DctA	curated:CharProtDB::CH_014038	curated:TCDB::P96603	curated:TCDB::Q1J1H5	curated:TCDB::Q848I3	curated:reanno::pseudo5_N2C3_1:AO356_18980	curated:SwissProt::Q9I4F5	curated:TCDB::Q01857
succinate-transport: dctA

# Ignore TCDB::A1JRS3 whose specificity seems to be unknown (although there is structural information)
dauA	succinate:H+ symporter DauA	curated:SwissProt::P0AFR2	ignore:TCDB::A1JRS3
succinate-transport: dauA

satP	succinate:H+ symporter SatP	curated:SwissProt::P0AC98
succinate-transport: satP

# TRAP transporter DctQMP.
# The P. aeruginosa system was not initially included (annotated as C4-dicarboxylate system; Q9HU16-8).
# Similarly for the system from Shewanella loihica PV-4 or P. stutzeri RCH2 (just one component annotated).
# The V. cholerae system is VC1927-VC1929 (PMID:22556361), but only the dctP
# (Q9KQR9) component is curated; Q9KQS0 is dctQ; Q9KQS1 is dctM.
# In Phaeobacter inhibens, the system is important for fumarate utilization:
# PGA1_c20670 = dctQ = I7EY26,
# PGA1_c20660 = dctM = I7DRS6,
# PGA1_c20680 = dctP = I7END8.
# Finally, ignore the system from S. amazonensis SB2B (Sama_2209:Sama_2211)
# as we have no fitness data for succinate from this organism (but it does utilize succinate).
dctQ	succinate TRAP transporter, small permease component DctQ	curated:SwissProt::O07837	curated:SwissProt::Q9HU17	curated:reanno::PV4:5208944	curated:reanno::psRCH2:GFF4196	uniprot:Q9KQS0	ignore:reanno::SB2B:6938089	uniprot:I7EY26

dctM	succinate TRAP transporter, large permease protein DctM	curated:SwissProt::O07838	curated:SwissProt::Q9HU16	curated:reanno::PV4:5208943	uniprot:Q9KQS1	ignore:reanno::SB2B:6938090	uniprot:I7DRS6

# B. subtilis DctB is similar to DctP but is probably involved in sensing, not transport, so is not included.
# Q2IUT5 = RPB_3329, A3QCW5 = Shew_1446 = 5208945, and Q8ECK4 = SO_3134 were shown to bind succinate (PMC4310620).
dctP	succinate TRAP transporter, component DctP	curated:SwissProt::P37735	curated:SwissProt::Q9HU18	curated:reanno::PV4:5208945	curated:SwissProt::Q9KQR9	ignore:reanno::SB2B:6938088	uniprot:I7END8	uniprot:Q2IUT5	uniprot:Q8ECK4
succinate-transport: dctQ dctM dctP

# 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).
Dshi_1194	TRAP transporter for succinate, fumarate, L-malate, and 2-oxoglutarate, fused 4TM/12TM components	uniprot:A8LI82	uniprot:E4PQE4

Dshi_1195	TRAP transporter for succinate, fumarate, L-malate, and 2-oxoglutarate, substrate-binding component	uniprot:A8LI83	uniprot:E4PQE3

succinate-transport: Dshi_1194 Dshi_1195

# Ignore mitochondrial dicarboxylate:phosphate antiporters
# Ignore antiporters dcuA/dcuB (i.e., fumarate:succinate antiport does not facilitate utilization of succinate)
# Ignore antiporters ttdT/citT (i.e., tartarte:succinate antiport does not facilitate utilization of succinate)
# Ignore mitochondrial succinate/fumarate antiporters
# Ignore succinate dehydrogenase components
# Ignore mitochondrial citrate/succinate antiporter
# Ignore succinate exporter SucE1 / TMEM184B
# Ignore succinate efflux transporter DcuC (although it acts as a succinate:proton symporter,
# so maybe it could suffice)

all: succinate-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
the source code
instructions for running GapMind on your computer

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