L-threonine catabolism in Pleomorphomonas diazotrophica R5-392

GapMind for catabolism of small carbon sources

L-threonine catabolism in Pleomorphomonas diazotrophica R5-392

Best path

braC, braD, braE, braF, braG, ltaE, adh, ackA, pta, 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 (46 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	CXZ10_RS02245	CXZ10_RS02250
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	CXZ10_RS02220	CXZ10_RS20565
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	CXZ10_RS02225
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	CXZ10_RS02230	CXZ10_RS13695
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	CXZ10_RS02235	CXZ10_RS20580
ltaE	L-threonine aldolase	CXZ10_RS18925	CXZ10_RS10540
adh	acetaldehyde dehydrogenase (not acylating)	CXZ10_RS19950	CXZ10_RS06795
ackA	acetate kinase	CXZ10_RS08810
pta	phosphate acetyltransferase	CXZ10_RS08805
gcvP	glycine cleavage system, P component (glycine decarboxylase)	CXZ10_RS18160	CXZ10_RS18165
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	CXZ10_RS18175
gcvH	glycine cleavage system, H component (lipoyl protein)	CXZ10_RS18170
lpd	dihydrolipoyl dehydrogenase	CXZ10_RS02855	CXZ10_RS14050
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	CXZ10_RS16385
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	CXZ10_RS16385
acs	acetyl-CoA synthetase, AMP-forming	CXZ10_RS16265
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	CXZ10_RS06795
aldA	lactaldehyde dehydrogenase	CXZ10_RS19950	CXZ10_RS13775
D-LDH	D-lactate dehydrogenase	CXZ10_RS01560	CXZ10_RS11675
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component	CXZ10_RS18525
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	CXZ10_RS18520
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	CXZ10_RS11675
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	CXZ10_RS11675
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	CXZ10_RS04300
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	CXZ10_RS16645	CXZ10_RS12115
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
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	CXZ10_RS04155	CXZ10_RS06940
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	CXZ10_RS20745
L-LDH	L-lactate dehydrogenase	CXZ10_RS14080	CXZ10_RS03470
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	CXZ10_RS16430
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	CXZ10_RS09405
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	CXZ10_RS18515
lldF	L-lactate dehydrogenase, LldF subunit	CXZ10_RS18520
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	CXZ10_RS18515
lutB	L-lactate dehydrogenase, LutB subunit	CXZ10_RS18520
lutC	L-lactate dehydrogenase, LutC subunit	CXZ10_RS18525
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
pccA	propionyl-CoA carboxylase, alpha subunit	CXZ10_RS06450	CXZ10_RS16310
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	CXZ10_RS06450	CXZ10_RS16310
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	CXZ10_RS16310
pccB	propionyl-CoA carboxylase, beta subunit
pco	propanyl-CoA oxidase
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	CXZ10_RS18020
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
RR42_RS28305	L-threonine:H+ symporter	CXZ10_RS00650
serP1	L-threonine uptake transporter SerP1	CXZ10_RS00650
snatA	L-threonine transporter snatA	CXZ10_RS02620
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	CXZ10_RS06580	CXZ10_RS07730
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase	CXZ10_RS00940
tdh	L-threonine 3-dehydrogenase	CXZ10_RS06080	CXZ10_RS02320
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	CXZ10_RS12325

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