L-threonine catabolism in Oleispira antarctica

GapMind for catabolism of small carbon sources

L-threonine catabolism in Oleispira antarctica

Best path

tdcC, ltaE, ald-dh-CoA, gcvP, gcvT, gcvH, lpd

Rules

Overview: L-threonine degradation in GapMind is based on MetaCyc pathway I via 2-ketobutyrate formate-lyase (link), pathway II via glycine (link), pathway III via methylglyoxal (link), and pathway IV via threonine aldolase (link). Pathway V is not thought to occur in prokaryotes and is not included.

all:

threonine-transport, tdcB, tdcE and propionyl-CoA-degradation
or threonine-transport, tdh, kbl and glycine-degradation
or threonine-transport, tdh, tynA and methylglyoxal-degradation
or threonine-transport, ltaE, acetaldehyde-degradation and glycine-degradation
Comment: 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.) 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. In L-threonine degradation III, tdh forms L-2-amino-3-oxobutanoate, and oxidase tynA forms methylglyoxal. In L-threonine degradation IV, aldolase ltaE cleaves threonine to acetaldehyde and glycine.

L-lactate-degradation:

L-LDH
or lldE, lldF and lldG
or lutA, lutB and lutC
or DVU3033 and DVU3032
or lctO and acs
or lctO, ackA and pta
Comment: Various L-lactate dehydrogenases are known, with different numbers of subunits; these all form pyruvate. Or, after L-lactate oxidase (lctO) forms acetate, the acetate is activated to acetyl-CoA.

methylglyoxal-degradation:

gloA, gloB and D-lactate-dehydrogenase
or yvgN, aldA and L-lactate-degradation
Comment: In methylglyoxal degradation I (link), 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. In methylglyoxal degradation IV (link), yvgN reduces methylglyoxal to (S)-lactaldehyde, aldA oxidizes it to (S)-lactate (also known as L-lactate).

D-lactate-dehydrogenase:

D-LDH
or lctB, lctC and lctD
or glcD, glcE and glcF
Comment: 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. 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.

glycine-degradation:

glycine-reductase and ackA
or glycine-reductase and pta
or gcvP, gcvT, gcvH and lpd
Comment: 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) Or glycine can cleaved to ammonia, CO2, and 5,10-methylene-tetrahydrofolate by the glycine cleavage system, gcvPTH/lpd.

glycine-reductase: grdA, grdE, grdB, grdD and grdC
acetaldehyde-degradation:

ald-dh-CoA
or adh and acs
or adh, ackA and pta
Comment: Acetaldehyde can be oxidized to acetyl-CoA, or oxidized to acetate and activated to acetyl-CoA by either acetyl-CoA synthetase (acs) or by acetate kinase (ackA) and phosphate acetyltransferase (pta).

propionyl-CoA-degradation:

prpC, prpD, acn and prpB
or prpC, acnD, prpF, acn and prpB
or propionyl-CoA-carboxylase, epi and methylmalonyl-CoA-mutase
or pco, hpcD, dddA and iolA
Comment: In 2-methylcitrate cycle I, propionyl-CoA is combined with oxalacetate (by prpC) to give methylcitrate, dehydrated to cis-2-methylaconitate by prpD, hydrated to (2R,3S)-2-methylisocitrate, and a lyase produces pyruvate and succinate. (We consider succinate as a central intermediate, as most organisms can activate it to succinyl-CoA or can oxidize it to fumarate and convert that to oxaloacetate.) In 2-methylcitrate cycle II, a different dehydratase (acnD) and an isomerase (prpF) replace the dehydratase prpD; acnD dehydrates (2S,3S)-2-methylcitrate to 2-methyl-trans-aconitate, and prpF isomerizes it to cis-2-methylaconitate. In propanoyl CoA degradation I, propionyl-CoA carboxylase forms (S)-methylmalonyl-CoA, methylmalonyl-CoA epimerase forms (R)-methylmalonyl-CoA, and methylmalonyl-CoA mutase forms succinyl-CoA, which is a central metabolite. (Note that methylmalonyl-CoA mutase requires adenosylcobamide, a form of vitamin B12, for activity.) In propanoyl-CoA degradation II: propionyl-CoA is oxidized to acrylyl-CoA by pco, hydrated to 3-hydroxypropionyl-CoA, hydrolzed to 3-hydroxypropionate, oxidized to 3-oxopropionate (malonate semialdehyde), and oxidized to acetyl-CoA and CO2.

methylmalonyl-CoA-mutase:

mcmA
or mcm-large and mcm-small
Comment: methylmalonyl-CoA mutase has a catalytic domain and a B12-binding domain. These are usually found in the same protein, which we call mcmA. In Metallosphaera and Pyrococcus, the B12-binding domain is a separate subunit. In Propionibacterium and Methylorubrum, there is an additional subunit with a catalytic domain only; this may have a protective role (PMID:14734568) and is not described here. There's also a mcm-interacting GTPase (known as MeaB or YgfD) that loads B12 onto mcm and protects it from inactivation (see PMC4631608); this is not described here. Some fused mcm proteins include a MeaB domain as well (i.e., Q8F222, Q8Y2U5).

propionyl-CoA-carboxylase:

pccA and pccB
or pccA1, pccA2 and pccB
Comment: propionyl-CoA carboxylase is a heteromer, usually with alpha and beta subunits pccAB. Haloferax mediterranei has a third subunit as well (pccX), which is not described here. Acidianus brierleyi has a diverged pccA split into two pieces.

threonine-transport:

braC, braD, braE, braF and braG
or tdcC
or sstT
or serP1
or phtA
or snatA
or RR42_RS28305
Comment: Transporters were identified using query: transporter:threonine:L-threonine:thr

70 steps (35 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
tdcC	L-threonine:H+ symporter TdcC
ltaE	L-threonine aldolase	OLEAN_RS17405
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	OLEAN_RS05730
gcvP	glycine cleavage system, P component (glycine decarboxylase)	OLEAN_RS13085
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	OLEAN_RS13075
gcvH	glycine cleavage system, H component (lipoyl protein)	OLEAN_RS13080
lpd	dihydrolipoyl dehydrogenase	OLEAN_RS08545	OLEAN_RS09175
Alternative steps:
ackA	acetate kinase	OLEAN_RS11860	OLEAN_RS14445
acn	(2R,3S)-2-methylcitrate dehydratase	OLEAN_RS05010	OLEAN_RS11565
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	OLEAN_RS05010
acs	acetyl-CoA synthetase, AMP-forming	OLEAN_RS11725	OLEAN_RS19275
adh	acetaldehyde dehydrogenase (not acylating)	OLEAN_RS18035	OLEAN_RS05730
aldA	lactaldehyde dehydrogenase	OLEAN_RS18035	OLEAN_RS01640
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	OLEAN_RS18860
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	OLEAN_RS03225	OLEAN_RS02280
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	OLEAN_RS18845	OLEAN_RS03220
D-LDH	D-lactate dehydrogenase	OLEAN_RS18180	OLEAN_RS18185
dddA	3-hydroxypropionate dehydrogenase	OLEAN_RS17440	OLEAN_RS18030
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	OLEAN_RS05320
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	OLEAN_RS15490
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	OLEAN_RS18205	OLEAN_RS04940
grdA	glycine reductase component A1
grdB	glycine reductase component B, gamma subunit
grdC	glycine reductase component C, beta subunit
grdD	glycine reductase component C, alpha subunit
grdE	glycine reductase component B, precursor to alpha/beta subunits
hpcD	3-hydroxypropionyl-CoA dehydratase	OLEAN_RS07250	OLEAN_RS10755
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	OLEAN_RS18035
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	OLEAN_RS06540
L-LDH	L-lactate dehydrogenase
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	OLEAN_RS09615
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	OLEAN_RS18180
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit
lutB	L-lactate dehydrogenase, LutB subunit
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	OLEAN_RS05325
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	OLEAN_RS05325	OLEAN_RS10290
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	OLEAN_RS05325
pccA	propionyl-CoA carboxylase, alpha subunit	OLEAN_RS02940	OLEAN_RS07665
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	OLEAN_RS07665	OLEAN_RS02940
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	OLEAN_RS02925	OLEAN_RS05310
pco	propanyl-CoA oxidase
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	OLEAN_RS08510
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	OLEAN_RS11865	OLEAN_RS05710
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	OLEAN_RS17970
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	OLEAN_RS12240	OLEAN_RS05740
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)

Confidence: high confidence medium confidence low confidence
transporter – transporters and PTS systems are shaded because predicting their specificity is particularly challenging.

This GapMind analysis is from Sep 24 2021. The underlying query database was built on Sep 17 2021.

Downloads

Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
SQLite3 databases

Related tools

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