L-threonine catabolism in Bacillus cytotoxicus NVH 391-98

Best path

RR42_RS28305, tdcB, tdcE, prpC, prpD, 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 (45 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
RR42_RS28305	L-threonine:H+ symporter	BCER98_RS03275	BCER98_RS12245
tdcB	L-threonine dehydratase	BCER98_RS07615
tdcE	2-ketobutyrate formate-lyase	BCER98_RS02455
prpC	2-methylcitrate synthase	BCER98_RS08940	BCER98_RS16525
prpD	2-methylcitrate dehydratase	BCER98_RS08945
acn	(2R,3S)-2-methylcitrate dehydratase	BCER98_RS11520
prpB	2-methylisocitrate lyase	BCER98_RS04725	BCER98_RS08950
Alternative steps:
ackA	acetate kinase	BCER98_RS16685
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BCER98_RS11520
acs	acetyl-CoA synthetase, AMP-forming	BCER98_RS16795	BCER98_RS09355
adh	acetaldehyde dehydrogenase (not acylating)	BCER98_RS11350	BCER98_RS07770
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	BCER98_RS04295	BCER98_RS11350
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BCER98_RS05485	BCER98_RS02040
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BCER98_RS01250	BCER98_RS19175
D-LDH	D-lactate dehydrogenase	BCER98_RS11280	BCER98_RS05540
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	BCER98_RS05575
epi	methylmalonyl-CoA epimerase
gcvH	glycine cleavage system, H component (lipoyl protein)	BCER98_RS18140
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BCER98_RS14715	BCER98_RS14710
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BCER98_RS14720
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BCER98_RS05540	BCER98_RS11280
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BCER98_RS05540
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BCER98_RS05535
gloA	glyoxylase I
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BCER98_RS15075
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	BCER98_RS09345	BCER98_RS16270
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BCER98_RS08965	BCER98_RS11350
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BCER98_RS03025	BCER98_RS14245
L-LDH	L-lactate dehydrogenase	BCER98_RS17615	BCER98_RS07790
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BCER98_RS16260
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BCER98_RS05540	BCER98_RS11280
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	BCER98_RS05570
lldF	L-lactate dehydrogenase, LldF subunit	BCER98_RS05575
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	BCER98_RS13515	BCER98_RS14440
ltaE	L-threonine aldolase	BCER98_RS19335
lutA	L-lactate dehydrogenase, LutA subunit	BCER98_RS05570	BCER98_RS05535
lutB	L-lactate dehydrogenase, LutB subunit	BCER98_RS05575
lutC	L-lactate dehydrogenase, LutC subunit	BCER98_RS05580
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
pccA	propionyl-CoA carboxylase, alpha subunit	BCER98_RS14535	BCER98_RS09330
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BCER98_RS14535	BCER98_RS09330
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BCER98_RS09350
pco	propanyl-CoA oxidase	BCER98_RS19470	BCER98_RS19465
phtA	L-threonine uptake permease PhtA
prpF	methylaconitate isomerase	BCER98_RS09685
pta	phosphate acetyltransferase	BCER98_RS19675	BCER98_RS14455
serP1	L-threonine uptake transporter SerP1	BCER98_RS03275	BCER98_RS12245
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	BCER98_RS03030	BCER98_RS08485
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BCER98_RS01155	BCER98_RS14145

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.