L-threonine catabolism in Cobetia crustatorum JO1

Best path

braC, braD, braE, braF, braG, tdcB, tdcE, prpC, acnD, prpF, acn, prpB

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 (43 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)	BF12_RS0108990
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BF12_RS0108995	BF12_RS0105635
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BF12_RS0109000
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BF12_RS0109005	BF12_RS0105650
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BF12_RS0109010	BF12_RS0105645
tdcB	L-threonine dehydratase	BF12_RS0106330	BF12_RS20845
tdcE	2-ketobutyrate formate-lyase
prpC	2-methylcitrate synthase	BF12_RS0111395	BF12_RS0111715
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BF12_RS0111390	BF12_RS0104480
prpF	methylaconitate isomerase	BF12_RS0111385	BF12_RS0111115
acn	(2R,3S)-2-methylcitrate dehydratase	BF12_RS0111390	BF12_RS0108445
prpB	2-methylisocitrate lyase	BF12_RS0104320	BF12_RS0111400
Alternative steps:
ackA	acetate kinase
acs	acetyl-CoA synthetase, AMP-forming	BF12_RS0102090	BF12_RS0100005
adh	acetaldehyde dehydrogenase (not acylating)	BF12_RS0101560	BF12_RS0106720
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	BF12_RS0105190	BF12_RS0105380
D-LDH	D-lactate dehydrogenase	BF12_RS0112005	BF12_RS0114565
dddA	3-hydroxypropionate dehydrogenase	BF12_RS0108230	BF12_RS0105385
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase
gcvH	glycine cleavage system, H component (lipoyl protein)	BF12_RS0106880
gcvP	glycine cleavage system, P component (glycine decarboxylase)
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BF12_RS0106870	BF12_RS0109250
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BF12_RS0112005
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BF12_RS0107000
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BF12_RS0107005
gloA	glyoxylase I	BF12_RS0116960	BF12_RS0114840
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BF12_RS0100045	BF12_RS0109405
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	BF12_RS0108390	BF12_RS0105565
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BF12_RS0110995	BF12_RS0108380
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BF12_RS0113080	BF12_RS0102810
L-LDH	L-lactate dehydrogenase	BF12_RS0113740
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BF12_RS0112445
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component
lctO	L-lactate oxidase or 2-monooxygenase	BF12_RS0113740
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	BF12_RS0111680	BF12_RS0104275
ltaE	L-threonine aldolase	BF12_RS0109265	BF12_RS0104015
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
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BF12_RS0112865
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
pccA	propionyl-CoA carboxylase, alpha subunit	BF12_RS0108265	BF12_RS0101835
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BF12_RS0101980	BF12_RS0101835
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	BF12_RS0107760
pccB	propionyl-CoA carboxylase, beta subunit	BF12_RS0108275
pco	propanyl-CoA oxidase	BF12_RS0108280
phtA	L-threonine uptake permease PhtA
prpD	2-methylcitrate dehydratase	BF12_RS0111380
pta	phosphate acetyltransferase	BF12_RS0112365
RR42_RS28305	L-threonine:H+ symporter	BF12_RS0110280
serP1	L-threonine uptake transporter SerP1	BF12_RS0110280
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	BF12_RS0113075	BF12_RS0116650
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BF12_RS0110115	BF12_RS0103180

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.