L-threonine catabolism in Rhizobium subbaraonis JC85

Best path

braC, braD, braE, braF, braG, ltaE, adh, acs, 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 (47 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)	CRO48_RS14965	CRO48_RS23625
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	CRO48_RS14940	CRO48_RS25805
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	CRO48_RS14945	CRO48_RS25800
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	CRO48_RS24445	CRO48_RS14950
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	CRO48_RS24440	CRO48_RS25020
ltaE	L-threonine aldolase	CRO48_RS05810	CRO48_RS10685
adh	acetaldehyde dehydrogenase (not acylating)	CRO48_RS25640	CRO48_RS28755
acs	acetyl-CoA synthetase, AMP-forming	CRO48_RS06990	CRO48_RS06980
gcvP	glycine cleavage system, P component (glycine decarboxylase)	CRO48_RS16230
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	CRO48_RS16220	CRO48_RS14885
gcvH	glycine cleavage system, H component (lipoyl protein)	CRO48_RS16225
lpd	dihydrolipoyl dehydrogenase	CRO48_RS07775	CRO48_RS09680
Alternative steps:
ackA	acetate kinase	CRO48_RS28905	CRO48_RS17315
acn	(2R,3S)-2-methylcitrate dehydratase	CRO48_RS08010
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	CRO48_RS08010
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	CRO48_RS02530
aldA	lactaldehyde dehydrogenase	CRO48_RS21435	CRO48_RS03095
D-LDH	D-lactate dehydrogenase	CRO48_RS12105	CRO48_RS20560
dddA	3-hydroxypropionate dehydrogenase	CRO48_RS26120	CRO48_RS00035
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	CRO48_RS23145
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	CRO48_RS00515	CRO48_RS20560
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	CRO48_RS00520	CRO48_RS20560
glcF	D-lactate dehydrogenase, FeS subunit GlcF	CRO48_RS00525
gloA	glyoxylase I	CRO48_RS09000	CRO48_RS14870
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	CRO48_RS18240	CRO48_RS23875
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	CRO48_RS03545	CRO48_RS05245
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	CRO48_RS21935	CRO48_RS18700
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	CRO48_RS23660	CRO48_RS18095
L-LDH	L-lactate dehydrogenase	CRO48_RS03015	CRO48_RS17805
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	CRO48_RS18355	CRO48_RS22475
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	CRO48_RS12105	CRO48_RS00515
lctO	L-lactate oxidase or 2-monooxygenase	CRO48_RS03015	CRO48_RS25565
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit
lutB	L-lactate dehydrogenase, LutB subunit
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	CRO48_RS14045
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	CRO48_RS14045
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	CRO48_RS14045
pccA	propionyl-CoA carboxylase, alpha subunit	CRO48_RS05745	CRO48_RS20780
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	CRO48_RS10170	CRO48_RS20880
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	CRO48_RS14060	CRO48_RS05735
pco	propanyl-CoA oxidase	CRO48_RS11515
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	CRO48_RS21855	CRO48_RS14280
prpC	2-methylcitrate synthase	CRO48_RS09445
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	CRO48_RS25060
pta	phosphate acetyltransferase	CRO48_RS28900	CRO48_RS17310
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	CRO48_RS09295
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	CRO48_RS23205	CRO48_RS24210
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	CRO48_RS23655	CRO48_RS18705
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	CRO48_RS17440	CRO48_RS02800

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.