Definition of D-alanine catabolism

GapMind for catabolism of small carbon sources

Definition of D-alanine catabolism

# GapMind describes D-alanine catabolism via D-alanine dehydrogenase, which forms pyruvate.
# This reaction is part of the
# MetaCyc pathway for L-alanine catabolism via D-alanine (metacyc:ALADEG-PWY). In
# principle, D-alanine might also be catabolized via racemization to
# L-alanine and transamination to pyruvate, but this is not described
# here.

Pf6N2E2_5402	ABC transporter for D-Alanine, substrate-binding component	curated:reanno::pseudo6_N2E2:Pf6N2E2_5402

Pf6N2E2_5403	ABC transporter for D-Alanine, permease component 2	curated:reanno::pseudo6_N2E2:Pf6N2E2_5403

Pf6N2E2_5404	ABC transporter for D-Alanine, permease component 1	curated:reanno::pseudo6_N2E2:Pf6N2E2_5404

Pf6N2E2_5405	ABC transporter for D-Alanine, ATPase component	curated:reanno::pseudo6_N2E2:Pf6N2E2_5405

# Transporters were identified using:
# query: transporter:D-alanine:D-ala.
D-alanine-transport: Pf6N2E2_5402 Pf6N2E2_5403 Pf6N2E2_5404 Pf6N2E2_5405

# Spore germination proteins and B. subtilis ygqE, which is not really characterized, were ignored.

# An ABC transporter from Azospirillum brasilense, with 5
# components, was identified in the fitness data. (Just one component was in the reannotations.)
# MctP was missed by the clustering tool, but is annotated as transporting D-alanine
# (see PMC135354, Figure 4A, showing that D-alanine inhibits transport).
# A related protein, BPHYT_RS22245 (uniprot:B2T7V3), is involved in D-alanine utilization.
AZOBR_RS08235	D-alanine ABC transporter, permease component 1	curated:reanno::azobra:AZOBR_RS08235
AZOBR_RS08240	D-alanine ABC transporter, permease component 2	uniprot:G8ALI9
AZOBR_RS08245	D-alanine ABC transporter, ATPase component 1	uniprot:G8ALJ0
AZOBR_RS08250	D-alanine ABC transporter, ATPase component 2	uniprot:G8ALJ1
AZOBR_RS08260	D-alanine ABC transporter, substrate-binding component	uniprot:G8ALJ3
D-alanine-transport: AZOBR_RS08235 AZOBR_RS08240 AZOBR_RS08245 AZOBR_RS08250 AZOBR_RS08260

cycA	D-alanine:H+ symporter CycA	curated:SwissProt::A0A0H2VDI7	curated:SwissProt::P0AAE0	curated:TCDB::F2HQ24	curated:TCDB::M1IW84	curated:reanno::WCS417:GFF1065	curated:reanno::pseudo3_N2E3:AO353_16120	curated:reanno::pseudo5_N2C3_1:AO356_17670	curated:SwissProt::A2RI86

D-alanine-transport: cycA

mctP	D-alanine transporter MctP	curated:TCDB::Q8VM88	curated:SwissProt::Q1M7A2	uniprot:B2T7V3
D-alanine-transport: mctP

dadA	D-alanine dehydrogenase	term:D-alanine%dehydrogenase

all: D-alanine-transport dadA

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Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
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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