Definition of L-threonine catabolism

GapMind for catabolism of small carbon sources

Definition of L-threonine catabolism

# L-threonine degradation in GapMind is based on MetaCyc
# pathway I via 2-ketobutyrate formate-lyase (metacyc:PWY-5437),
# pathway II via glycine (metacyc:THREONINE-DEG2-PWY),
# pathway III via methylglyoxal (metacyc:THRDLCTCAT-PWY),
# and pathway IV via threonine aldolase (metacyc:PWY-5436).
# Pathway V is not thought to occur in prokaryotes and is not included.

# ABC transporters: BraCDEFG from Pseudomonas aeruginosa and LivJFGHM from Streptococcus pneumoniae.
# A related system, NatABCDE from Anabaena PCC 7120 (transporter N-I), is also thought to transport threonine
# (see PMC177005; the genes are in TC 3.A.1.4.6).
# These are all described by the rules for braCDEFG.
import alanine.steps:braC braD braE braF braG

# Transporters were identified using
# query: transporter:threonine:L-threonine:thr
threonine-transport: braC braD braE braF braG

tdcC	L-threonine:H+ symporter TdcC	curated:SwissProt::P0AAD8
threonine-transport: tdcC

sstT	L-threonine:Na+ symporter SstT	curated:SwissProt::P0AGE4
threonine-transport: sstT

# A closely related protein (uniprot:A2RI87) is annotated as a serine permease only
serP1	L-threonine uptake transporter SerP1	curated:TCDB::F2HQ25	ignore:SwissProt::A2RI87
threonine-transport: serP1

phtA	L-threonine uptake permease PhtA	curated:TCDB::Q5ZY33
threonine-transport: phtA

snatA	L-threonine transporter snatA	curated:TCDB::Q8J305
threonine-transport: snatA

# Specifically important for threonine utilization, and downstream of kbl and tdh.
# Homologs are D/L-alanine or serine:H+ symporters
# (i.e., E. coli cycA)
RR42_RS28305	L-threonine:H+ symporter	uniprot:A0A0C4YRF7
threonine-transport: RR42_RS28305

# Serine/threonine exchangers, exporters, and non-specific metazoan transporters were ignored.

# propionyl-CoA is a common intermediate in threonine degradation
import propionate.steps:propionyl-CoA-degradation

# Acetaldehyde is an intermediate in threonine degradation.
# Also ackA (acetate kinase) and pta are involved in consuming acetyl phosphate.
import ethanol.steps:acetaldehyde-degradation ackA pta

# glycine is an intermediate in threonine utilization

grdA	glycine reductase component A1	curated:BRENDA::P26971	curated:BRENDA::Q185M6	curated:metacyc::MONOMER-13142	curated:metacyc::MONOMER-20600	ignore_other:1.21.4.2

grdE	glycine reductase component B, precursor to alpha/beta subunits	curated:BRENDA::Q9R4G7	ignore_other:1.21.4.2

grdB	glycine reductase component B, gamma subunit	curated:CharProtDB::CH_090869	ignore_other:1.21.4.2

grdD	glycine reductase component C, alpha subunit	curated:CharProtDB::CH_013101	ignore_other:1.21.4.2

grdC	glycine reductase component C, beta subunit	curated:CharProtDB::CH_017328	ignore_other:1.21.4.2

glycine-reductase: grdA grdE grdB grdD grdC

# Glycine can be reduced to acetyl phosphate by glycine reductase (EC:1.21.4.2), and then
# converted to acetate (by ackA in reverse) or acetyl-CoA (by pta)
glycine-degradation: glycine-reductase ackA
glycine-degradation: glycine-reductase pta

# Sometimes the H component is given this EC number as well.
gcvP	glycine cleavage system, P component (glycine decarboxylase)	EC:1.4.4.2	ignore:SwissProt::P23434	ignore:SwissProt::P25855
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	EC:2.1.2.10
gcvH	glycine cleavage system, H component (lipoyl protein)	term:Glycine cleavage system H	term:glycine decarboxylase H
lpd	dihydrolipoyl dehydrogenase	EC:1.8.1.4

# Or glycine can cleaved to ammonia, CO2, and 5,10-methylene-tetrahydrofolate
# by the glycine cleavage system, gcvPTH/lpd.
glycine-degradation: gcvP gcvT gcvH lpd

# methylglyoxal is an intermediate in threonine degradation.

# Ignore the protein fragment P84719
gloA	glyoxylase I	EC:4.4.1.5	ignore:SwissProt::P84719
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	EC:3.1.2.6

import D-lactate.steps:D-lactate-dehydrogenase

# In methylglyoxal degradation I (metacyc:PWY-5386),
# gloA condenses methylglyoxal with glutathione to
# (R)-S-lactoylglutathione, gloB cleaves it to D-lactate (also known as
# (R)-lactate) and glutathione, and the lactate is oxidized to
# pyruvate.
methylglyoxal-degradation: gloA gloB D-lactate-dehydrogenase

# MetaCyc Pathway: methylglyoxal degradation II is not thought to
# occur in prokaryotes and is not described here.

# MetaCyc Pathway: methylglyoxal degradation III involves reduction to
# hydroxyacetone and then to (S)-propane-1,2-diol.  This does not lead
# to any usable carbon and is not described here.

# 1.1.1.184 describes relatively non-specific ketone reductases, some of which are related to
# methylglyoxal reductases and may well have that activity as well.
yvgN	methylglyoxal reductase (NADPH-dependent)	EC:1.1.1.283	ignore_other:1.1.1.184
import rhamnose.steps:aldA # lactaldehyde dehydrogenase

import L-lactate.steps:L-lactate-degradation

# In methylglyoxal degradation IV (metacyc:PWY-5459), yvgN reduces
# methylglyoxal to (S)-lactaldehyde, aldA oxidizes it to (S)-lactate (also known as
# L-lactate).
methylglyoxal-degradation: yvgN aldA L-lactate-degradation

# MetaCyc Pathway: methylglyoxal degradation V is very similar to
# pathway IV but with a different L-lactate dehydrogenase.

# MetaCyc Pathway: methylglyoxal degradation VI
# is not thought to occur in prokaryotes and is not described here.

# MetaCyc Pathway: methylglyoxal degradation VII involves a
# methylglyoxal oxidase that converts it to pyruvate. This pathway is
# not thought to occur in prokaryotes and is not described here.

# CH_124219 is annotated as this but without the EC number
tdcB	L-threonine dehydratase	EC:4.3.1.19	curated:CharProtDB::CH_124219
# This reaction is not linked to an EC number.
# E. coli tdcB (PF42632) and pflB (P09373) seem to be the only ones that are characterized.
# Many pyruvate-formate lyases (EC 2.3.1.54) can probably carry out this reaction, so they are ignored.
tdcE	2-ketobutyrate formate-lyase	curated:SwissProt::P42632	curated:BRENDA::P09373	ignore_other:2.3.1.54

# In L-threonine degradation I, threonine dehydratase (tdcB)
# forms 2-iminbutanoate, which is deaminated
# to 2-oxobutanoate (either by the same enzyme or by ridA);
# then formate-lyase (tdcE) converts this to propanoyl-CoA.
# (MetaCyc also includes conversion to propanoate, which forms ATP, but this does not allow for
# growth unless the formate can be utilized.)
all: threonine-transport tdcB tdcE propionyl-CoA-degradation

tdh	L-threonine 3-dehydrogenase	EC:1.1.1.103
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	EC:2.3.1.29

# In L-threonine degradation II, a dehydrogenase (tdh)
# forms L-2-amino-3-oxobutanoate, and a C-acetyltransferase (kbl)
# cleaves this to acetyl-CoA and glycine.
all: threonine-transport tdh kbl glycine-degradation


tynA	aminoacetone oxidase	EC:1.4.3.21

# In L-threonine degradation III, tdh forms L-2-amino-3-oxobutanoate,
# and oxidase tynA forms methylglyoxal.
all: threonine-transport tdh tynA methylglyoxal-degradation

# Some serine hydroxymethyltransferases (glyA) are reported to carry out
# the L-threonine aldolase reaction, but the Km are high (see PMC219072 or PMID:22141341).
# CharProtDB::CH_123166 is annotated as threonine aldolase but without the EC number, and is nearly identical to 
# O13427, which is a low-specificity threonine aldolase.
ltaE	L-threonine aldolase	EC:4.1.2.5	EC:4.1.2.48	ignore:SwissProt::P0A825	ignore:SwissProt::D3DKC4	ignore:CharProtDB::CH_123166

# In L-threonine degradation IV, aldolase ltaE
# cleaves threonine to acetaldehyde and glycine.
all: threonine-transport ltaE acetaldehyde-degradation glycine-degradation

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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 preprint 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