L-threonine catabolism in Rhizobium leguminosarum 3841

Best path

braC, braD, braE, braF, braG, tdh, tynA, gloA*, gloB, glcD, glcE, glcF

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 (49 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)	RL_RS19315	RL_RS18225
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	RL_RS19340	RL_RS34940
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	RL_RS19335	RL_RS14690
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	RL_RS19330	RL_RS14685
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	RL_RS19325	RL_RS14680
tdh	L-threonine 3-dehydrogenase	RL_RS17540	RL_RS28050
tynA	aminoacetone oxidase	RL_RS15680
gloA*	glyoxylase I	RL_RS22000 with RL_RS35910	RL_RS01895
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	RL_RS17810	RL_RS22380
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	RL_RS04515	RL_RS16805
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	RL_RS04520
glcF	D-lactate dehydrogenase, FeS subunit GlcF	RL_RS04525
Alternative steps:
ackA	acetate kinase	RL_RS20135	RL_RS09830
acn	(2R,3S)-2-methylcitrate dehydratase	RL_RS23365
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	RL_RS23365
acs	acetyl-CoA synthetase, AMP-forming	RL_RS24320	RL_RS25385
adh	acetaldehyde dehydrogenase (not acylating)	RL_RS14170	RL_RS21990
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	RL_RS31855	RL_RS18615
D-LDH	D-lactate dehydrogenase	RL_RS16805	RL_RS33825
dddA	3-hydroxypropionate dehydrogenase	RL_RS31805	RL_RS36730
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	RL_RS08930
gcvH	glycine cleavage system, H component (lipoyl protein)	RL_RS13260
gcvP	glycine cleavage system, P component (glycine decarboxylase)	RL_RS13265
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	RL_RS13255	RL_RS32485
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	RL_RS01945	RL_RS09490
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	RL_RS04070	RL_RS18615
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	RL_RS17545	RL_RS22590
L-LDH	L-lactate dehydrogenase	RL_RS18435	RL_RS22890
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	RL_RS28380
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	RL_RS28375	RL_RS35510
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	RL_RS04515	RL_RS04995
lctO	L-lactate oxidase or 2-monooxygenase	RL_RS18435	RL_RS02310
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	RL_RS28930	RL_RS11630
ltaE	L-threonine aldolase	RL_RS21085	RL_RS08395
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	RL_RS27330
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	RL_RS27330
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	RL_RS27330
pccA	propionyl-CoA carboxylase, alpha subunit	RL_RS13185	RL_RS28870
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	RL_RS13185	RL_RS10835
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	RL_RS28870
pccB	propionyl-CoA carboxylase, beta subunit	RL_RS13210	RL_RS28875
pco	propanyl-CoA oxidase	RL_RS31715
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	RL_RS03990	RL_RS23010
prpC	2-methylcitrate synthase	RL_RS11570	RL_RS12925
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	RL_RS14730
pta	phosphate acetyltransferase	RL_RS02125	RL_RS13790
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	RL_RS12380
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	RL_RS10150	RL_RS24215
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
yvgN	methylglyoxal reductase (NADPH-dependent)	RL_RS23475	RL_RS33475

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.