L-threonine catabolism in Sinorhizobium medicae WSM419

Best path

braC, braD, braE, braF, braG, 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 (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)	SMED_RS11940	SMED_RS02690
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	SMED_RS11965	SMED_RS26550
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	SMED_RS11960
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	SMED_RS11955	SMED_RS14380
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	SMED_RS11950	SMED_RS26555
ltaE	L-threonine aldolase	SMED_RS13585	SMED_RS04060
adh	acetaldehyde dehydrogenase (not acylating)	SMED_RS23160	SMED_RS24290
ackA	acetate kinase	SMED_RS23375
pta	phosphate acetyltransferase	SMED_RS24255	SMED_RS23370
gcvP	glycine cleavage system, P component (glycine decarboxylase)	SMED_RS05910
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	SMED_RS05920	SMED_RS16645
gcvH	glycine cleavage system, H component (lipoyl protein)	SMED_RS05915
lpd	dihydrolipoyl dehydrogenase	SMED_RS14175	SMED_RS05405
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	SMED_RS15470	SMED_RS01825
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	SMED_RS15470	SMED_RS01825
acs	acetyl-CoA synthetase, AMP-forming	SMED_RS16020	SMED_RS16030
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	SMED_RS01125	SMED_RS12210
D-LDH	D-lactate dehydrogenase	SMED_RS10130	SMED_RS12405
dddA	3-hydroxypropionate dehydrogenase	SMED_RS14400	SMED_RS18130
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	SMED_RS04515
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	SMED_RS01975	SMED_RS10130
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	SMED_RS01980	SMED_RS22705
glcF	D-lactate dehydrogenase, FeS subunit GlcF	SMED_RS01985
gloA	glyoxylase I	SMED_RS07255	SMED_RS12000
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	SMED_RS19785	SMED_RS11185
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	SMED_RS17950	SMED_RS11005
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	SMED_RS01625	SMED_RS22390
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	SMED_RS11110	SMED_RS14460
L-LDH	L-lactate dehydrogenase	SMED_RS22470	SMED_RS14785
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	SMED_RS30595
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	SMED_RS30600	SMED_RS12685
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	SMED_RS01975	SMED_RS10130
lctO	L-lactate oxidase or 2-monooxygenase	SMED_RS17650	SMED_RS22470
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	SMED_RS21215
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	SMED_RS21215	SMED_RS25330
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	SMED_RS21215
pccA	propionyl-CoA carboxylase, alpha subunit	SMED_RS21220	SMED_RS22680
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	SMED_RS21220	SMED_RS04740
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	SMED_RS15755
pccB	propionyl-CoA carboxylase, beta subunit	SMED_RS21225	SMED_RS22670
pco	propanyl-CoA oxidase	SMED_RS23355
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	SMED_RS01540
prpC	2-methylcitrate synthase	SMED_RS05715
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	SMED_RS06180
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	SMED_RS06855	SMED_RS18550
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	SMED_RS11105	SMED_RS10620
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	SMED_RS02905	SMED_RS10005

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 Apr 09 2024. The underlying query database was built on Sep 17 2021.