L-threonine catabolism in Luteipulveratus mongoliensis MN07-A0370

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 (52 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)	VV02_RS14190
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	VV02_RS14195
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	VV02_RS14200
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	VV02_RS14205	VV02_RS16280
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	VV02_RS14210	VV02_RS16285
ltaE	L-threonine aldolase	VV02_RS07835	VV02_RS19430
adh	acetaldehyde dehydrogenase (not acylating)	VV02_RS10095	VV02_RS09595
ackA	acetate kinase	VV02_RS25000
pta	phosphate acetyltransferase	VV02_RS25005
gcvP	glycine cleavage system, P component (glycine decarboxylase)	VV02_RS15390
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	VV02_RS17055
gcvH	glycine cleavage system, H component (lipoyl protein)	VV02_RS15365
lpd	dihydrolipoyl dehydrogenase	VV02_RS13485	VV02_RS17070
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	VV02_RS16300
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	VV02_RS16300
acs	acetyl-CoA synthetase, AMP-forming	VV02_RS23465	VV02_RS05940
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	VV02_RS00495	VV02_RS10095
D-LDH	D-lactate dehydrogenase	VV02_RS18345	VV02_RS12700
dddA	3-hydroxypropionate dehydrogenase	VV02_RS21410
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	VV02_RS06850
epi	methylmalonyl-CoA epimerase	VV02_RS19290
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	VV02_RS12700	VV02_RS18345
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	VV02_RS12695
glcF	D-lactate dehydrogenase, FeS subunit GlcF	VV02_RS12690
gloA	glyoxylase I
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	VV02_RS15155	VV02_RS07285
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	VV02_RS10365	VV02_RS19060
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	VV02_RS18370	VV02_RS16495
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	VV02_RS18680	VV02_RS02285
L-LDH	L-lactate dehydrogenase	VV02_RS23790	VV02_RS16415
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	VV02_RS19050
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	VV02_RS19045
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	VV02_RS18345	VV02_RS12700
lctO	L-lactate oxidase or 2-monooxygenase	VV02_RS16415	VV02_RS23790
lldE	L-lactate dehydrogenase, LldE subunit	VV02_RS06855
lldF	L-lactate dehydrogenase, LldF subunit	VV02_RS06850
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	VV02_RS06855	VV02_RS12690
lutB	L-lactate dehydrogenase, LutB subunit	VV02_RS06850
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	VV02_RS12940	VV02_RS19245
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	VV02_RS09685	VV02_RS12940
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	VV02_RS12940	VV02_RS19245
pccA	propionyl-CoA carboxylase, alpha subunit	VV02_RS10230	VV02_RS05075
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	VV02_RS11015	VV02_RS10230
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	VV02_RS05075
pccB	propionyl-CoA carboxylase, beta subunit	VV02_RS10350	VV02_RS05795
pco	propanyl-CoA oxidase	VV02_RS21565	VV02_RS19870
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	VV02_RS11725	VV02_RS21385
prpC	2-methylcitrate synthase	VV02_RS20325	VV02_RS17100
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
RR42_RS28305	L-threonine:H+ symporter	VV02_RS18730	VV02_RS08520
serP1	L-threonine uptake transporter SerP1	VV02_RS18730	VV02_RS08520
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	VV02_RS19315	VV02_RS25925
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	VV02_RS18675	VV02_RS13525
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	VV02_RS10235	VV02_RS24475

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.