L-threonine catabolism in Pseudovibrio axinellae Ad2

Best path

braC, braD, braE, braF, braG, tdcB, tdcE, pccA, pccB, epi, mcm-large, mcm-small

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 (49 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)	PsAD2_RS02810	PsAD2_RS07425
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	PsAD2_RS07415	PsAD2_RS02835
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	PsAD2_RS02830	PsAD2_RS07420
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	PsAD2_RS07405	PsAD2_RS02825
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	PsAD2_RS07410	PsAD2_RS02820
tdcB	L-threonine dehydratase	PsAD2_RS16680	PsAD2_RS17155
tdcE	2-ketobutyrate formate-lyase	PsAD2_RS10840
pccA	propionyl-CoA carboxylase, alpha subunit	PsAD2_RS02130	PsAD2_RS22235
pccB	propionyl-CoA carboxylase, beta subunit	PsAD2_RS02145	PsAD2_RS22230
epi	methylmalonyl-CoA epimerase	PsAD2_RS01440
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	PsAD2_RS04560	PsAD2_RS15690
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	PsAD2_RS04560	PsAD2_RS15690
Alternative steps:
ackA	acetate kinase	PsAD2_RS00020	PsAD2_RS14055
acn	(2R,3S)-2-methylcitrate dehydratase	PsAD2_RS01920
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	PsAD2_RS01920
acs	acetyl-CoA synthetase, AMP-forming	PsAD2_RS07830	PsAD2_RS06350
adh	acetaldehyde dehydrogenase (not acylating)	PsAD2_RS08775	PsAD2_RS20005
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	PsAD2_RS20005
aldA	lactaldehyde dehydrogenase	PsAD2_RS08865	PsAD2_RS20650
D-LDH	D-lactate dehydrogenase	PsAD2_RS03695	PsAD2_RS11590
dddA	3-hydroxypropionate dehydrogenase	PsAD2_RS05370	PsAD2_RS08720
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
gcvH	glycine cleavage system, H component (lipoyl protein)	PsAD2_RS11270
gcvP	glycine cleavage system, P component (glycine decarboxylase)	PsAD2_RS11280	PsAD2_RS11275
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	PsAD2_RS11265	PsAD2_RS02455
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	PsAD2_RS21985	PsAD2_RS03695
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	PsAD2_RS21990
glcF	D-lactate dehydrogenase, FeS subunit GlcF	PsAD2_RS21995
gloA	glyoxylase I	PsAD2_RS10690	PsAD2_RS01300
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	PsAD2_RS04330	PsAD2_RS01670
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	PsAD2_RS08800	PsAD2_RS16425
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	PsAD2_RS05090	PsAD2_RS08865
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	PsAD2_RS12155	PsAD2_RS17290
L-LDH	L-lactate dehydrogenase	PsAD2_RS05700	PsAD2_RS09095
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	PsAD2_RS07855
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	PsAD2_RS21985	PsAD2_RS03695
lctO	L-lactate oxidase or 2-monooxygenase	PsAD2_RS05700
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	PsAD2_RS19485	PsAD2_RS06985
ltaE	L-threonine aldolase	PsAD2_RS06125	PsAD2_RS16635
lutA	L-lactate dehydrogenase, LutA subunit
lutB	L-lactate dehydrogenase, LutB subunit
lutC	L-lactate dehydrogenase, LutC subunit
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	PsAD2_RS04560	PsAD2_RS15690
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	PsAD2_RS02130	PsAD2_RS01215
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	PsAD2_RS08770
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	PsAD2_RS12285	PsAD2_RS18050
prpC	2-methylcitrate synthase	PsAD2_RS01570
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	PsAD2_RS13785
pta	phosphate acetyltransferase	PsAD2_RS00025	PsAD2_RS14060
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	PsAD2_RS10665
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC	PsAD2_RS19180	PsAD2_RS17040
tdh	L-threonine 3-dehydrogenase	PsAD2_RS12700	PsAD2_RS20005
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	PsAD2_RS22385	PsAD2_RS17955

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.