L-threonine catabolism in Skermanella stibiiresistens SB22

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 (55 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)	N825_RS03725	N825_RS03285
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	N825_RS03260	N825_RS16515
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	N825_RS03265	N825_RS05145
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	N825_RS03270	N825_RS24020
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	N825_RS03275	N825_RS15205
tdcB	L-threonine dehydratase	N825_RS25840	N825_RS19980
tdcE	2-ketobutyrate formate-lyase	N825_RS21670
pccA	propionyl-CoA carboxylase, alpha subunit	N825_RS12620	N825_RS14790
pccB	propionyl-CoA carboxylase, beta subunit	N825_RS12625	N825_RS14800
epi	methylmalonyl-CoA epimerase	N825_RS04235
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	N825_RS12610	N825_RS29330
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	N825_RS12610	N825_RS29330
Alternative steps:
ackA	acetate kinase	N825_RS32490	N825_RS20750
acn	(2R,3S)-2-methylcitrate dehydratase	N825_RS22455	N825_RS26795
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	N825_RS26795
acs	acetyl-CoA synthetase, AMP-forming	N825_RS11705	N825_RS11835
adh	acetaldehyde dehydrogenase (not acylating)	N825_RS20855	N825_RS19970
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	N825_RS32720	N825_RS01910
D-LDH	D-lactate dehydrogenase	N825_RS23825	N825_RS31190
dddA	3-hydroxypropionate dehydrogenase	N825_RS19355	N825_RS01915
DVU3032	L-lactate dehydrogenase, LutC-like component	N825_RS12120	N825_RS31155
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	N825_RS31155	N825_RS12115
gcvH	glycine cleavage system, H component (lipoyl protein)	N825_RS27600
gcvP	glycine cleavage system, P component (glycine decarboxylase)	N825_RS27610	N825_RS27605
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	N825_RS27595	N825_RS01950
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	N825_RS27050	N825_RS23825
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	N825_RS27055	N825_RS23825
glcF	D-lactate dehydrogenase, FeS subunit GlcF	N825_RS27060
gloA	glyoxylase I	N825_RS04355	N825_RS17510
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	N825_RS19725	N825_RS30920
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	N825_RS27875	N825_RS33380
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	N825_RS35530	N825_RS01910
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	N825_RS17300	N825_RS16015
L-LDH	L-lactate dehydrogenase	N825_RS06060	N825_RS07905
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	N825_RS16365
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	N825_RS16370	N825_RS29295
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	N825_RS27050	N825_RS23825
lctO	L-lactate oxidase or 2-monooxygenase	N825_RS06060
lldE	L-lactate dehydrogenase, LldE subunit	N825_RS12110	N825_RS31150
lldF	L-lactate dehydrogenase, LldF subunit	N825_RS31155	N825_RS12115
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	N825_RS05030	N825_RS27325
ltaE	L-threonine aldolase	N825_RS06375	N825_RS01965
lutA	L-lactate dehydrogenase, LutA subunit	N825_RS31150	N825_RS12110
lutB	L-lactate dehydrogenase, LutB subunit	N825_RS31155	N825_RS12115
lutC	L-lactate dehydrogenase, LutC subunit	N825_RS31160
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	N825_RS12610	N825_RS29330
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	N825_RS12620	N825_RS14735
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	N825_RS18065
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	N825_RS06105	N825_RS32770
prpC	2-methylcitrate synthase	N825_RS04360
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	N825_RS23490	N825_RS34365
pta	phosphate acetyltransferase	N825_RS32495	N825_RS20745
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	N825_RS01840
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	N825_RS07075	N825_RS34055
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	N825_RS32280	N825_RS09505

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.