L-threonine catabolism in Bacillus horneckiae 1P01SC

Best path

sstT, 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 (52 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
sstT	L-threonine:Na+ symporter SstT	CWS20_RS13245
ltaE	L-threonine aldolase	CWS20_RS21050	CWS20_RS14545
adh	acetaldehyde dehydrogenase (not acylating)	CWS20_RS10330	CWS20_RS13150
ackA	acetate kinase	CWS20_RS01815	CWS20_RS25205
pta	phosphate acetyltransferase	CWS20_RS14775	CWS20_RS25195
gcvP	glycine cleavage system, P component (glycine decarboxylase)	CWS20_RS10995	CWS20_RS11000
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	CWS20_RS11005
gcvH	glycine cleavage system, H component (lipoyl protein)	CWS20_RS00700
lpd	dihydrolipoyl dehydrogenase	CWS20_RS05475	CWS20_RS25210
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	CWS20_RS08780
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	CWS20_RS08780
acs	acetyl-CoA synthetase, AMP-forming	CWS20_RS23850	CWS20_RS10745
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	CWS20_RS13130
aldA	lactaldehyde dehydrogenase	CWS20_RS10330	CWS20_RS13150
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	CWS20_RS00580
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	CWS20_RS00575	CWS20_RS25735
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	CWS20_RS12830	CWS20_RS25730
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	CWS20_RS00565	CWS20_RS12835
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	CWS20_RS00560	CWS20_RS12840
D-LDH	D-lactate dehydrogenase	CWS20_RS12615	CWS20_RS16185
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	CWS20_RS12590
epi	methylmalonyl-CoA epimerase	CWS20_RS25285	CWS20_RS23175
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	CWS20_RS05235	CWS20_RS16185
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	CWS20_RS05225
glcF	D-lactate dehydrogenase, FeS subunit GlcF	CWS20_RS05230	CWS20_RS16180
gloA	glyoxylase I	CWS20_RS16335	CWS20_RS01730
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	CWS20_RS11075	CWS20_RS21105
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	CWS20_RS04890	CWS20_RS08920
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	CWS20_RS13650	CWS20_RS20855
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	CWS20_RS08810
L-LDH	L-lactate dehydrogenase	CWS20_RS02065	CWS20_RS11585
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	CWS20_RS06480	CWS20_RS04040
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	CWS20_RS16185	CWS20_RS05235
lctO	L-lactate oxidase or 2-monooxygenase	CWS20_RS11585
lldE	L-lactate dehydrogenase, LldE subunit	CWS20_RS12585
lldF	L-lactate dehydrogenase, LldF subunit	CWS20_RS12590
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	CWS20_RS12585
lutB	L-lactate dehydrogenase, LutB subunit	CWS20_RS12590
lutC	L-lactate dehydrogenase, LutC subunit	CWS20_RS12595
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	CWS20_RS25240	CWS20_RS14670
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	CWS20_RS25240
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	CWS20_RS25240	CWS20_RS14670
pccA	propionyl-CoA carboxylase, alpha subunit	CWS20_RS25120	CWS20_RS05610
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	CWS20_RS25120	CWS20_RS21840
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	CWS20_RS25290	CWS20_RS21850
pco	propanyl-CoA oxidase	CWS20_RS14685	CWS20_RS14680
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	CWS20_RS11820	CWS20_RS01460
prpC	2-methylcitrate synthase	CWS20_RS01450	CWS20_RS02055
prpD	2-methylcitrate dehydratase	CWS20_RS01455
prpF	methylaconitate isomerase
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA
tdcB	L-threonine dehydratase	CWS20_RS03590
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	CWS20_RS08805	CWS20_RS18590
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	CWS20_RS24585	CWS20_RS10805

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.