L-threonine catabolism in Knoellia flava TL1

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 (45 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)
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	N798_RS14385	N798_RS04795
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	N798_RS14380
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	N798_RS14375	N798_RS04780
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	N798_RS14370	N798_RS04785
ltaE	L-threonine aldolase	N798_RS15100	N798_RS15885
adh	acetaldehyde dehydrogenase (not acylating)	N798_RS09860	N798_RS04170
ackA	acetate kinase	N798_RS12265
pta	phosphate acetyltransferase	N798_RS12270
gcvP	glycine cleavage system, P component (glycine decarboxylase)	N798_RS07580
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	N798_RS08140	N798_RS16010
gcvH	glycine cleavage system, H component (lipoyl protein)	N798_RS07605
lpd	dihydrolipoyl dehydrogenase	N798_RS15180	N798_RS08165
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	N798_RS04670
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	N798_RS04670
acs	acetyl-CoA synthetase, AMP-forming	N798_RS12905	N798_RS01730
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	N798_RS09790	N798_RS09860
D-LDH	D-lactate dehydrogenase	N798_RS10165	N798_RS16845
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	N798_RS07065
epi	methylmalonyl-CoA epimerase	N798_RS16035
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	N798_RS10165
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	N798_RS10165
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	N798_RS07725	N798_RS14350
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	N798_RS14785	N798_RS16580
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	N798_RS06805	N798_RS09860
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	N798_RS12980
L-LDH	L-lactate dehydrogenase	N798_RS00730	N798_RS16710
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	N798_RS16595
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	N798_RS10165
lctO	L-lactate oxidase or 2-monooxygenase	N798_RS00730
lldE	L-lactate dehydrogenase, LldE subunit	N798_RS07060
lldF	L-lactate dehydrogenase, LldF subunit	N798_RS07065
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	N798_RS07060
lutB	L-lactate dehydrogenase, LutB subunit	N798_RS07065
lutC	L-lactate dehydrogenase, LutC subunit	N798_RS07070
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	N798_RS05935	N798_RS15965
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	N798_RS05935	N798_RS15965
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	N798_RS05935	N798_RS05435
pccA	propionyl-CoA carboxylase, alpha subunit	N798_RS09750	N798_RS16330
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	N798_RS09750	N798_RS16330
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	N798_RS09605	N798_RS09655
pco	propanyl-CoA oxidase	N798_RS07895	N798_RS03280
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	N798_RS13855	N798_RS06285
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	N798_RS09475
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	N798_RS12960	N798_RS10430
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	N798_RS09735

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.