L-threonine catabolism in Verminephrobacter eiseniae EF01-2

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 (46 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)	VEIS_RS09140	VEIS_RS23860
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	VEIS_RS09145	VEIS_RS14585
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	VEIS_RS09150	VEIS_RS14580
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	VEIS_RS22515	VEIS_RS19725
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	VEIS_RS09160	VEIS_RS02980
ltaE	L-threonine aldolase	VEIS_RS08225	VEIS_RS20545
adh	acetaldehyde dehydrogenase (not acylating)	VEIS_RS13090	VEIS_RS17035
acs	acetyl-CoA synthetase, AMP-forming	VEIS_RS15655	VEIS_RS01310
gcvP	glycine cleavage system, P component (glycine decarboxylase)	VEIS_RS19170	VEIS_RS12025
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	VEIS_RS19160	VEIS_RS19610
gcvH	glycine cleavage system, H component (lipoyl protein)	VEIS_RS19165
lpd	dihydrolipoyl dehydrogenase	VEIS_RS09370	VEIS_RS19250
Alternative steps:
ackA	acetate kinase
acn	(2R,3S)-2-methylcitrate dehydratase	VEIS_RS06560	VEIS_RS21070
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	VEIS_RS06560
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	VEIS_RS13550	VEIS_RS03235
aldA	lactaldehyde dehydrogenase	VEIS_RS10335	VEIS_RS24010
D-LDH	D-lactate dehydrogenase	VEIS_RS00130	VEIS_RS18330
dddA	3-hydroxypropionate dehydrogenase	VEIS_RS04460	VEIS_RS21860
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	VEIS_RS16535
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	VEIS_RS03065	VEIS_RS00130
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	VEIS_RS16095	VEIS_RS10185
glcF	D-lactate dehydrogenase, FeS subunit GlcF	VEIS_RS16090
gloA	glyoxylase I	VEIS_RS13165
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	VEIS_RS02890	VEIS_RS19480
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	VEIS_RS08860	VEIS_RS17305
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	VEIS_RS21480	VEIS_RS17125
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)
L-LDH	L-lactate dehydrogenase	VEIS_RS15460	VEIS_RS07450
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	VEIS_RS22715	VEIS_RS10230
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	VEIS_RS00130	VEIS_RS03065
lctO	L-lactate oxidase or 2-monooxygenase	VEIS_RS14990	VEIS_RS15460
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	VEIS_RS16490
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	VEIS_RS16490
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	VEIS_RS16490
pccA	propionyl-CoA carboxylase, alpha subunit	VEIS_RS16510	VEIS_RS04150
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	VEIS_RS16510	VEIS_RS07255
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	VEIS_RS16500	VEIS_RS20540
pco	propanyl-CoA oxidase	VEIS_RS08445
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	VEIS_RS15010	VEIS_RS03195
prpC	2-methylcitrate synthase	VEIS_RS21540	VEIS_RS25725
prpD	2-methylcitrate dehydratase	VEIS_RS03200
prpF	methylaconitate isomerase	VEIS_RS01490	VEIS_RS00830
pta	phosphate acetyltransferase	VEIS_RS19355	VEIS_RS03945
RR42_RS28305	L-threonine:H+ symporter	VEIS_RS13795
serP1	L-threonine uptake transporter SerP1	VEIS_RS13795
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	VEIS_RS01510	VEIS_RS10515
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	VEIS_RS00565	VEIS_RS17275
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.