L-threonine catabolism in Tistlia consotensis USBA 355

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 (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)	B9O00_RS11400	B9O00_RS19590
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	B9O00_RS11425	B9O00_RS18240
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	B9O00_RS11420	B9O00_RS18235
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	B9O00_RS11415	B9O00_RS18780
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	B9O00_RS11410	B9O00_RS19570
ltaE	L-threonine aldolase	B9O00_RS22365	B9O00_RS11385
adh	acetaldehyde dehydrogenase (not acylating)	B9O00_RS05420	B9O00_RS20310
acs	acetyl-CoA synthetase, AMP-forming	B9O00_RS28395	B9O00_RS29560
gcvP	glycine cleavage system, P component (glycine decarboxylase)	B9O00_RS03400
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	B9O00_RS03410	B9O00_RS12275
gcvH	glycine cleavage system, H component (lipoyl protein)	B9O00_RS03405
lpd	dihydrolipoyl dehydrogenase	B9O00_RS29400	B9O00_RS06970
Alternative steps:
ackA	acetate kinase
acn	(2R,3S)-2-methylcitrate dehydratase	B9O00_RS08500
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	B9O00_RS08500
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	B9O00_RS10030	B9O00_RS15630
D-LDH	D-lactate dehydrogenase	B9O00_RS04045	B9O00_RS13275
dddA	3-hydroxypropionate dehydrogenase	B9O00_RS30525	B9O00_RS20305
DVU3032	L-lactate dehydrogenase, LutC-like component	B9O00_RS07670
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	B9O00_RS07675
epi	methylmalonyl-CoA epimerase	B9O00_RS12535
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	B9O00_RS02030	B9O00_RS04045
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	B9O00_RS02025	B9O00_RS04045
glcF	D-lactate dehydrogenase, FeS subunit GlcF	B9O00_RS02015
gloA	glyoxylase I	B9O00_RS17695	B9O00_RS09940
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	B9O00_RS02230	B9O00_RS09155
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	B9O00_RS03145	B9O00_RS14075
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	B9O00_RS16490	B9O00_RS00790
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	B9O00_RS00625
L-LDH	L-lactate dehydrogenase	B9O00_RS16355	B9O00_RS06995
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	B9O00_RS02060
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	B9O00_RS04045	B9O00_RS02030
lctO	L-lactate oxidase or 2-monooxygenase	B9O00_RS16355
lldE	L-lactate dehydrogenase, LldE subunit	B9O00_RS07680
lldF	L-lactate dehydrogenase, LldF subunit	B9O00_RS07675
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	B9O00_RS07680
lutB	L-lactate dehydrogenase, LutB subunit	B9O00_RS07675
lutC	L-lactate dehydrogenase, LutC subunit	B9O00_RS07670
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	B9O00_RS16560	B9O00_RS14900
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	B9O00_RS16560	B9O00_RS14900
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	B9O00_RS16560	B9O00_RS14900
pccA	propionyl-CoA carboxylase, alpha subunit	B9O00_RS17565	B9O00_RS18055
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	B9O00_RS17565	B9O00_RS24495
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	B9O00_RS18055
pccB	propionyl-CoA carboxylase, beta subunit	B9O00_RS17560	B9O00_RS06440
pco	propanyl-CoA oxidase	B9O00_RS18005	B9O00_RS18920
phtA	L-threonine uptake permease PhtA	B9O00_RS18350
prpB	2-methylisocitrate lyase	B9O00_RS29010
prpC	2-methylcitrate synthase	B9O00_RS25450	B9O00_RS09950
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	B9O00_RS18815	B9O00_RS03595
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	B9O00_RS14755
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	B9O00_RS17765	B9O00_RS21430
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	B9O00_RS06960	B9O00_RS11945
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	B9O00_RS11940	B9O00_RS06115

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.