L-threonine catabolism in Pseudomonas baetica a390

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 (53 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)	C0J26_RS09040
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	C0J26_RS09035
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	C0J26_RS09030
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	C0J26_RS09025	C0J26_RS03610
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	C0J26_RS09020	C0J26_RS03600
ltaE	L-threonine aldolase	C0J26_RS28220	C0J26_RS10670
adh	acetaldehyde dehydrogenase (not acylating)	C0J26_RS18005	C0J26_RS27190
ackA	acetate kinase	C0J26_RS06130
pta	phosphate acetyltransferase	C0J26_RS05350
gcvP	glycine cleavage system, P component (glycine decarboxylase)	C0J26_RS20855	C0J26_RS29550
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	C0J26_RS20865	C0J26_RS29560
gcvH	glycine cleavage system, H component (lipoyl protein)	C0J26_RS29555	C0J26_RS20850
lpd	dihydrolipoyl dehydrogenase	C0J26_RS19760	C0J26_RS25195
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	C0J26_RS24615	C0J26_RS11685
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	C0J26_RS24615	C0J26_RS25345
acs	acetyl-CoA synthetase, AMP-forming	C0J26_RS10580	C0J26_RS06710
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	C0J26_RS12950	C0J26_RS27190
D-LDH	D-lactate dehydrogenase	C0J26_RS04615	C0J26_RS10970
dddA	3-hydroxypropionate dehydrogenase	C0J26_RS15680	C0J26_RS28395
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	C0J26_RS04625
epi	methylmalonyl-CoA epimerase	C0J26_RS26785
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	C0J26_RS11180
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	C0J26_RS11175
glcF	D-lactate dehydrogenase, FeS subunit GlcF	C0J26_RS11170
gloA	glyoxylase I	C0J26_RS14980
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	C0J26_RS11975	C0J26_RS08080
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	C0J26_RS15240	C0J26_RS15160
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	C0J26_RS04135	C0J26_RS04225
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	C0J26_RS02605
L-LDH	L-lactate dehydrogenase	C0J26_RS23155
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	C0J26_RS26420
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	C0J26_RS11180
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	C0J26_RS04630
lldF	L-lactate dehydrogenase, LldF subunit	C0J26_RS04625
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	C0J26_RS04630
lutB	L-lactate dehydrogenase, LutB subunit	C0J26_RS04625
lutC	L-lactate dehydrogenase, LutC subunit	C0J26_RS04620
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	C0J26_RS17000	C0J26_RS25630
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	C0J26_RS30885	C0J26_RS03790
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	C0J26_RS25615
pco	propanyl-CoA oxidase	C0J26_RS00745	C0J26_RS15235
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	C0J26_RS24625	C0J26_RS16655
prpC	2-methylcitrate synthase	C0J26_RS24620	C0J26_RS19795
prpD	2-methylcitrate dehydratase	C0J26_RS24605
prpF	methylaconitate isomerase	C0J26_RS24610
RR42_RS28305	L-threonine:H+ symporter	C0J26_RS21710	C0J26_RS20455
serP1	L-threonine uptake transporter SerP1	C0J26_RS20455	C0J26_RS21710
snatA	L-threonine transporter snatA	C0J26_RS03750
sstT	L-threonine:Na+ symporter SstT	C0J26_RS17295
tdcB	L-threonine dehydratase	C0J26_RS29325	C0J26_RS13830
tdcC	L-threonine:H+ symporter TdcC	C0J26_RS11680	C0J26_RS05565
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	C0J26_RS09310	C0J26_RS27880
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	C0J26_RS18950	C0J26_RS17430

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.