L-threonine catabolism in Haloechinothrix alba DSM 45207

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 (48 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)	CHB84_RS21595
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	CHB84_RS21575	CHB84_RS11940
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	CHB84_RS21580	CHB84_RS11945
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	CHB84_RS21585	CHB84_RS02420
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	CHB84_RS21590	CHB84_RS06250
ltaE	L-threonine aldolase	CHB84_RS14645	CHB84_RS21135
adh	acetaldehyde dehydrogenase (not acylating)	CHB84_RS12510	CHB84_RS18820
acs	acetyl-CoA synthetase, AMP-forming	CHB84_RS13260	CHB84_RS09900
gcvP	glycine cleavage system, P component (glycine decarboxylase)	CHB84_RS10645
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	CHB84_RS21140	CHB84_RS03000
gcvH	glycine cleavage system, H component (lipoyl protein)	CHB84_RS10620
lpd	dihydrolipoyl dehydrogenase	CHB84_RS14995	CHB84_RS07340
Alternative steps:
ackA	acetate kinase
acn	(2R,3S)-2-methylcitrate dehydratase	CHB84_RS10720
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	CHB84_RS10720
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	CHB84_RS19465
aldA	lactaldehyde dehydrogenase	CHB84_RS02915	CHB84_RS12510
D-LDH	D-lactate dehydrogenase	CHB84_RS14550	CHB84_RS03225
dddA	3-hydroxypropionate dehydrogenase	CHB84_RS14690
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	CHB84_RS08445
epi	methylmalonyl-CoA epimerase	CHB84_RS02825
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	CHB84_RS14550	CHB84_RS07965
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	CHB84_RS14550
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	CHB84_RS09385	CHB84_RS08795
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	CHB84_RS03020	CHB84_RS21025
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	CHB84_RS05390	CHB84_RS02915
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	CHB84_RS07105
L-LDH	L-lactate dehydrogenase	CHB84_RS08565
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	CHB84_RS03130
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	CHB84_RS14550
lctO	L-lactate oxidase or 2-monooxygenase	CHB84_RS08565
lldE	L-lactate dehydrogenase, LldE subunit	CHB84_RS08450
lldF	L-lactate dehydrogenase, LldF subunit	CHB84_RS08445
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	CHB84_RS08450
lutB	L-lactate dehydrogenase, LutB subunit	CHB84_RS08445
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	CHB84_RS04570	CHB84_RS17275
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	CHB84_RS17275	CHB84_RS04570
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	CHB84_RS04570	CHB84_RS03660
pccA	propionyl-CoA carboxylase, alpha subunit	CHB84_RS04620	CHB84_RS20140
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	CHB84_RS16745	CHB84_RS04620
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	CHB84_RS15105
pccB	propionyl-CoA carboxylase, beta subunit	CHB84_RS04665	CHB84_RS20135
pco	propanyl-CoA oxidase	CHB84_RS03285
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	CHB84_RS03065
prpC	2-methylcitrate synthase	CHB84_RS11320	CHB84_RS11470
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	CHB84_RS04995
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	CHB84_RS02110	CHB84_RS11005
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	CHB84_RS13760	CHB84_RS03845
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	CHB84_RS10945

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 Apr 09 2024. The underlying query database was built on Sep 17 2021.