L-threonine catabolism in Acidovorax caeni R-24608

Best path

braC, braD, braE, braF, braG, ltaE, adh, acs, 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 (45 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)	BN2503_RS02255	BN2503_RS04725
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BN2503_RS02260	BN2503_RS06735
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BN2503_RS02265	BN2503_RS06730
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BN2503_RS02270	BN2503_RS06725
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BN2503_RS02275	BN2503_RS06720
ltaE	L-threonine aldolase	BN2503_RS13955
adh	acetaldehyde dehydrogenase (not acylating)	BN2503_RS13190	BN2503_RS03525
acs	acetyl-CoA synthetase, AMP-forming	BN2503_RS13075	BN2503_RS06015
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BN2503_RS15250
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BN2503_RS15260
gcvH	glycine cleavage system, H component (lipoyl protein)	BN2503_RS15255
lpd*	dihydrolipoyl dehydrogenase	BN2503_RS17105 with BN2503_RS11830	BN2503_RS03815
Alternative steps:
ackA	acetate kinase	BN2503_RS06830
acn	(2R,3S)-2-methylcitrate dehydratase	BN2503_RS02445	BN2503_RS11475
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BN2503_RS02445	BN2503_RS11475
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	BN2503_RS03525	BN2503_RS02410
D-LDH	D-lactate dehydrogenase	BN2503_RS02710	BN2503_RS14000
dddA	3-hydroxypropionate dehydrogenase	BN2503_RS07740	BN2503_RS06875
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	BN2503_RS07530
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BN2503_RS09085	BN2503_RS02710
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BN2503_RS07990	BN2503_RS02710
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BN2503_RS07980
gloA	glyoxylase I	BN2503_RS11640
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BN2503_RS10160	BN2503_RS07825
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	BN2503_RS05070	BN2503_RS04075
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BN2503_RS03555	BN2503_RS07195
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)
L-LDH	L-lactate dehydrogenase	BN2503_RS08065	BN2503_RS10025
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BN2503_RS01735
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BN2503_RS09085	BN2503_RS02710
lctO	L-lactate oxidase or 2-monooxygenase	BN2503_RS08720	BN2503_RS11200
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	BN2503_RS07510
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BN2503_RS07510
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BN2503_RS07510
pccA	propionyl-CoA carboxylase, alpha subunit	BN2503_RS07525	BN2503_RS06975
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BN2503_RS07525	BN2503_RS04310
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BN2503_RS07520	BN2503_RS06995
pco	propanyl-CoA oxidase	BN2503_RS01970
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BN2503_RS08680	BN2503_RS02435
prpC	2-methylcitrate synthase	BN2503_RS02450	BN2503_RS08525
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	BN2503_RS02440
pta	phosphate acetyltransferase	BN2503_RS06835	BN2503_RS03565
RR42_RS28305	L-threonine:H+ symporter	BN2503_RS07220	BN2503_RS15280
serP1	L-threonine uptake transporter SerP1	BN2503_RS07220	BN2503_RS15280
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	BN2503_RS12720	BN2503_RS15770
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BN2503_RS10275	BN2503_RS02325
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.