L-threonine catabolism in Cronobacter universalis NCTC 9529

Best path

sstT, 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 (42 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
sstT	L-threonine:Na+ symporter SstT	AFK65_RS02445
ltaE	L-threonine aldolase	AFK65_RS06840	AFK65_RS14720
adh	acetaldehyde dehydrogenase (not acylating)	AFK65_RS10715	AFK65_RS11195
ackA	acetate kinase	AFK65_RS13705	AFK65_RS11890
pta	phosphate acetyltransferase	AFK65_RS13710	AFK65_RS14350
gcvP	glycine cleavage system, P component (glycine decarboxylase)	AFK65_RS15930
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	AFK65_RS15940
gcvH	glycine cleavage system, H component (lipoyl protein)	AFK65_RS15935
lpd	dihydrolipoyl dehydrogenase	AFK65_RS03720	AFK65_RS00765
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	AFK65_RS03735	AFK65_RS11020
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	AFK65_RS11020
acs	acetyl-CoA synthetase, AMP-forming	AFK65_RS17415
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	AFK65_RS11195
aldA	lactaldehyde dehydrogenase	AFK65_RS10605	AFK65_RS08605
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	AFK65_RS18540
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	AFK65_RS18525
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	AFK65_RS18520
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	AFK65_RS18515	AFK65_RS10265
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	AFK65_RS18510	AFK65_RS10260
D-LDH	D-lactate dehydrogenase	AFK65_RS10685	AFK65_RS18935
dddA	3-hydroxypropionate dehydrogenase	AFK65_RS08790
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	AFK65_RS08935
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	AFK65_RS13240	AFK65_RS07090
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	AFK65_RS13570	AFK65_RS13905
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	AFK65_RS04445	AFK65_RS08795
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	AFK65_RS19285	AFK65_RS06320
L-LDH	L-lactate dehydrogenase	AFK65_RS00595	AFK65_RS10210
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
lctO	L-lactate oxidase or 2-monooxygenase	AFK65_RS00595
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
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	AFK65_RS01805	AFK65_RS10290
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	AFK65_RS01805	AFK65_RS10290
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	AFK65_RS10290
pccB	propionyl-CoA carboxylase, beta subunit
pco	propanyl-CoA oxidase
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	AFK65_RS17740
prpC	2-methylcitrate synthase	AFK65_RS06090
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	AFK65_RS19990
RR42_RS28305	L-threonine:H+ symporter	AFK65_RS00970	AFK65_RS17055
serP1	L-threonine uptake transporter SerP1	AFK65_RS17055	AFK65_RS03700
snatA	L-threonine transporter snatA	AFK65_RS11190
tdcB	L-threonine dehydratase	AFK65_RS00865
tdcC	L-threonine:H+ symporter TdcC	AFK65_RS15545
tdcE	2-ketobutyrate formate-lyase	AFK65_RS06960
tdh	L-threonine 3-dehydrogenase	AFK65_RS19280	AFK65_RS00460
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	AFK65_RS16755	AFK65_RS04135

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.