L-threonine catabolism in Chromobacterium vaccinii MWU205

Best path

tdcC, 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 (49 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
tdcC	L-threonine:H+ symporter TdcC	VL52_RS12080
ltaE	L-threonine aldolase	VL52_RS15620	VL52_RS11385
adh	acetaldehyde dehydrogenase (not acylating)	VL52_RS21455	VL52_RS06935
ackA	acetate kinase	VL52_RS15345	VL52_RS02270
pta	phosphate acetyltransferase	VL52_RS15350	VL52_RS02265
gcvP	glycine cleavage system, P component (glycine decarboxylase)	VL52_RS02865
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	VL52_RS02855
gcvH	glycine cleavage system, H component (lipoyl protein)	VL52_RS02860
lpd	dihydrolipoyl dehydrogenase	VL52_RS06780	VL52_RS01105
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	VL52_RS06920	VL52_RS16820
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	VL52_RS06920	VL52_RS13705
acs	acetyl-CoA synthetase, AMP-forming	VL52_RS11020	VL52_RS20355
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	VL52_RS13795
aldA	lactaldehyde dehydrogenase	VL52_RS07105	VL52_RS21455
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	VL52_RS09675	VL52_RS22490
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	VL52_RS15500
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	VL52_RS15495
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	VL52_RS15490	VL52_RS03360
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	VL52_RS15485	VL52_RS03360
D-LDH	D-lactate dehydrogenase	VL52_RS18670	VL52_RS20375
dddA	3-hydroxypropionate dehydrogenase	VL52_RS11315
DVU3032	L-lactate dehydrogenase, LutC-like component	VL52_RS18660
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	VL52_RS18665
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	VL52_RS20375	VL52_RS18670
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	VL52_RS13355	VL52_RS04985
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	VL52_RS05620	VL52_RS12240
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	VL52_RS18865	VL52_RS21030
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	VL52_RS11940	VL52_RS21020
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	VL52_RS13405	VL52_RS00340
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
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	VL52_RS20375
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	VL52_RS18655
lldF	L-lactate dehydrogenase, LldF subunit	VL52_RS18665
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	VL52_RS18655
lutB	L-lactate dehydrogenase, LutB subunit	VL52_RS18665
lutC	L-lactate dehydrogenase, LutC subunit	VL52_RS18660
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	VL52_RS19945	VL52_RS01580
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	VL52_RS01580	VL52_RS19945
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	VL52_RS19955
pco	propanyl-CoA oxidase	VL52_RS20895	VL52_RS19965
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	VL52_RS13445	VL52_RS06905
prpC	2-methylcitrate synthase	VL52_RS06910	VL52_RS01125
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	VL52_RS06925	VL52_RS07045
RR42_RS28305	L-threonine:H+ symporter	VL52_RS13800	VL52_RS00285
serP1	L-threonine uptake transporter SerP1	VL52_RS00290	VL52_RS00285
snatA	L-threonine transporter snatA	VL52_RS11865	VL52_RS00260
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	VL52_RS15040	VL52_RS10860
tdcE	2-ketobutyrate formate-lyase	VL52_RS12070
tdh	L-threonine 3-dehydrogenase	VL52_RS13400	VL52_RS10400
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	VL52_RS19845	VL52_RS14040

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.