Definition of D-lactate catabolism

GapMind for catabolism of small carbon sources

Definition of D-lactate catabolism

# D-lactate catabolism in GapMind is based on D-lactate dehydrogenases, which form pyruvate.

# 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.)
lctP	D-lactate:H+ symporter LctP or LidP	curated:SwissProt::P33231	curated:reanno::WCS417:GFF4712	curated:reanno::pseudo5_N2C3_1:AO356_07550	curated:TCDB::Q46839	uniprot:Q8EGS2	uniprot:L0GFN1

# Transporters were identified using
# query: transporter:D-lactate:(R)-lactate:D,L-lactic
D-lactate-transport: lctP

larD	D,L-lactic acid transporter	curated:SwissProt::F9UST3	curated:SwissProt::F9UMX3
D-lactate-transport: larD

mctP	D,L-lactic acid transporter	curated:TCDB::Q8VM88	curated:SwissProt::Q1M7A2
D-lactate-transport: mctP

PGA1_c12640	D-lactate ABC transporter, ATP-binding component	curated:reanno::Phaeo:GFF1248
PGA1_c12650	D-lactate ABC transporter, permease component 1	curated:reanno::Phaeo:GFF1249
PGA1_c12660	D-lactate ABC transporter, permease component 2	curated:reanno::Phaeo:GFF1250
PGA1_c12670	D-lactate ABC transporter, substrate-binding component	curated:reanno::Phaeo:GFF1251
D-lactate-transport: PGA1_c12640 PGA1_c12650 PGA1_c12660 PGA1_c12670

# F8SVK1 (TC 2.A.1.6.11) seems to be a weak lactate transporter, so ignore

# 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.
D-LDH	D-lactate dehydrogenase	EC:1.1.1.28	EC:1.1.99.6	EC:1.1.2.4	uniprot:Q8EGS3	curated:BRENDA::Q1GAA2	curated:BRENDA::Q48534

D-lactate-dehydrogenase: D-LDH

# lctB = Awo_c08710 is the small Etf subunit
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	curated:BRENDA::H6LBB0	ignore_other:1.3.1.110

# lctC = Awo_c08720 is the large Etf subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	curated:BRENDA::H6LBB1	ignore_other:1.3.1.110

# lctD = Awo_c08730 is the LDH subunit
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	curated:BRENDA::H6LBS1	ignore_other:1.3.1.110

# 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.
D-lactate-dehydrogenase: lctB lctC lctD

glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	curated:reanno::Cup4G11:RR42_RS17300	curated:reanno::Phaeo:GFF2925	curated:reanno::Smeli:SMc00832	curated:reanno::psRCH2:GFF3772	curated:SwissProt::P0AEP9	ignore_other:1.1.99.14

glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	curated:reanno::Cup4G11:RR42_RS17310	curated:reanno::Phaeo:GFF2924	curated:reanno::Smeli:SMc00833	curated:reanno::psRCH2:GFF3771	curated:SwissProt::P52073	ignore_other:1.1.99.14

glcF	D-lactate dehydrogenase, FeS subunit GlcF	curated:reanno::Cup4G11:RR42_RS17315	curated:reanno::Phaeo:GFF2923	curated:reanno::Smeli:SMc00926	curated:reanno::psRCH2:GFF3770	curated:SwissProt::P52074	ignore_other:1.1.99.14

# 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-dehydrogenase: glcD glcE glcF

all: D-lactate-transport D-lactate-dehydrogenase

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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