L-threonine catabolism in Azospirillum thiophilum BV-S

Best path

braC, braD, braE, braF, braG, tdcB, tdcE, prpC, acnD, prpF, acn, prpB

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)	AL072_RS29535	AL072_RS15665
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	AL072_RS29560	AL072_RS26405
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	AL072_RS29555	AL072_RS26410
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	AL072_RS29550	AL072_RS06650
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	AL072_RS29545	AL072_RS19865
tdcB	L-threonine dehydratase	AL072_RS17145	AL072_RS13045
tdcE	2-ketobutyrate formate-lyase	AL072_RS16680
prpC	2-methylcitrate synthase	AL072_RS10170	AL072_RS12620
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	AL072_RS10175	AL072_RS06770
prpF	methylaconitate isomerase	AL072_RS10180
acn	(2R,3S)-2-methylcitrate dehydratase	AL072_RS10175	AL072_RS16725
prpB	2-methylisocitrate lyase	AL072_RS23510	AL072_RS10185
Alternative steps:
ackA	acetate kinase	AL072_RS27185	AL072_RS00850
acs	acetyl-CoA synthetase, AMP-forming	AL072_RS06780	AL072_RS08155
adh	acetaldehyde dehydrogenase (not acylating)	AL072_RS23920	AL072_RS26875
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	AL072_RS26875
aldA	lactaldehyde dehydrogenase	AL072_RS26660	AL072_RS22360
D-LDH	D-lactate dehydrogenase	AL072_RS28785	AL072_RS00320
dddA	3-hydroxypropionate dehydrogenase	AL072_RS14630	AL072_RS25745
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	AL072_RS28775
epi	methylmalonyl-CoA epimerase	AL072_RS08275	AL072_RS14955
gcvH	glycine cleavage system, H component (lipoyl protein)	AL072_RS12755
gcvP	glycine cleavage system, P component (glycine decarboxylase)	AL072_RS12745	AL072_RS12750
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	AL072_RS12760
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	AL072_RS01910	AL072_RS00320
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	AL072_RS01905
glcF	D-lactate dehydrogenase, FeS subunit GlcF	AL072_RS01900
gloA	glyoxylase I	AL072_RS12645	AL072_RS21520
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	AL072_RS29060	AL072_RS15790
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	AL072_RS16240	AL072_RS03915
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	AL072_RS20255	AL072_RS23010
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	AL072_RS05630
L-LDH	L-lactate dehydrogenase	AL072_RS20270	AL072_RS27445
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	AL072_RS01125
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	AL072_RS01120	AL072_RS22415
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	AL072_RS00320	AL072_RS01910
lctO	L-lactate oxidase or 2-monooxygenase	AL072_RS18255	AL072_RS20270
lldE	L-lactate dehydrogenase, LldE subunit	AL072_RS28780
lldF	L-lactate dehydrogenase, LldF subunit	AL072_RS28775
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	AL072_RS12260	AL072_RS18800
ltaE	L-threonine aldolase	AL072_RS25945	AL072_RS09335
lutA	L-lactate dehydrogenase, LutA subunit	AL072_RS28780
lutB	L-lactate dehydrogenase, LutB subunit	AL072_RS28775
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	AL072_RS14880
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	AL072_RS14880
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	AL072_RS14880
pccA	propionyl-CoA carboxylase, alpha subunit	AL072_RS14875	AL072_RS28295
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	AL072_RS14875	AL072_RS09915
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	AL072_RS28295
pccB	propionyl-CoA carboxylase, beta subunit	AL072_RS14870	AL072_RS28305
pco	propanyl-CoA oxidase	AL072_RS24310
phtA	L-threonine uptake permease PhtA
prpD	2-methylcitrate dehydratase
pta	phosphate acetyltransferase	AL072_RS27180	AL072_RS00855
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	AL072_RS14900
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	AL072_RS26875	AL072_RS28930
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	AL072_RS30885	AL072_RS22840

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.