L-threonine catabolism in Rhizobium leguminosarum WSM1325

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 (46 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)	RLEG_RS16390	RLEG_RS15300
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	RLEG_RS16415	RLEG_RS27550
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	RLEG_RS16410	RLEG_RS30565
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	RLEG_RS16405	RLEG_RS27560
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	RLEG_RS16400	RLEG_RS23815
ltaE	L-threonine aldolase	RLEG_RS17865	RLEG_RS06210
adh	acetaldehyde dehydrogenase (not acylating)	RLEG_RS11275	RLEG_RS18780
acs	acetyl-CoA synthetase, AMP-forming	RLEG_RS21015	RLEG_RS21030
gcvP	glycine cleavage system, P component (glycine decarboxylase)	RLEG_RS10355
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	RLEG_RS10345	RLEG_RS26835
gcvH	glycine cleavage system, H component (lipoyl protein)	RLEG_RS10350
lpd	dihydrolipoyl dehydrogenase	RLEG_RS35115	RLEG_RS08935
Alternative steps:
ackA	acetate kinase	RLEG_RS17140
acn	(2R,3S)-2-methylcitrate dehydratase	RLEG_RS20100
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	RLEG_RS20100
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	RLEG_RS27460	RLEG_RS15650
D-LDH	D-lactate dehydrogenase	RLEG_RS13860	RLEG_RS02945
dddA	3-hydroxypropionate dehydrogenase	RLEG_RS27540	RLEG_RS25580
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	RLEG_RS06755
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	RLEG_RS02460	RLEG_RS13860
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	RLEG_RS02465
glcF	D-lactate dehydrogenase, FeS subunit GlcF	RLEG_RS02470
gloA*	glyoxylase I	RLEG_RS18790 with RLEG_RS24765	RLEG_RS22975
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	RLEG_RS14890	RLEG_RS19185
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	RLEG_RS23030	RLEG_RS26045
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	RLEG_RS02115	RLEG_RS15650
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	RLEG_RS14605	RLEG_RS19365
L-LDH	L-lactate dehydrogenase	RLEG_RS15510	RLEG_RS19670
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	RLEG_RS24455
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	RLEG_RS24450	RLEG_RS19085
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	RLEG_RS02460	RLEG_RS02945
lctO	L-lactate oxidase or 2-monooxygenase	RLEG_RS00425	RLEG_RS15510
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	RLEG_RS33135
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	RLEG_RS33135
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	RLEG_RS33135
pccA	propionyl-CoA carboxylase, alpha subunit	RLEG_RS10270	RLEG_RS35170
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	RLEG_RS10270	RLEG_RS08555
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	RLEG_RS10295	RLEG_RS35165
pco	propanyl-CoA oxidase	RLEG_RS27635
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	RLEG_RS02045	RLEG_RS19785
prpC	2-methylcitrate synthase	RLEG_RS08875	RLEG_RS10015
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	RLEG_RS00240	RLEG_RS10915
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	RLEG_RS09560
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	RLEG_RS07885	RLEG_RS20905
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	RLEG_RS14600	RLEG_RS24780
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	RLEG_RS20215	RLEG_RS13770

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.