L-threonine catabolism in Methylobacterium nodulans ORS 2060

Best path

RR42_RS28305, 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 (49 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
RR42_RS28305	L-threonine:H+ symporter	MNOD_RS23565	MNOD_RS04385
ltaE	L-threonine aldolase	MNOD_RS05645	MNOD_RS25045
adh	acetaldehyde dehydrogenase (not acylating)	MNOD_RS35765	MNOD_RS07620
acs	acetyl-CoA synthetase, AMP-forming	MNOD_RS24610	MNOD_RS10010
gcvP	glycine cleavage system, P component (glycine decarboxylase)	MNOD_RS28540
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	MNOD_RS28550	MNOD_RS16030
gcvH	glycine cleavage system, H component (lipoyl protein)	MNOD_RS28545
lpd	dihydrolipoyl dehydrogenase	MNOD_RS34000	MNOD_RS30760
Alternative steps:
ackA	acetate kinase	MNOD_RS02005	MNOD_RS32630
acn	(2R,3S)-2-methylcitrate dehydratase	MNOD_RS00820
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	MNOD_RS00820
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	MNOD_RS32090	MNOD_RS35765
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	MNOD_RS08385	MNOD_RS14755
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	MNOD_RS08415	MNOD_RS18715
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	MNOD_RS08410	MNOD_RS05615
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	MNOD_RS07445	MNOD_RS18705
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	MNOD_RS08395	MNOD_RS18700
D-LDH	D-lactate dehydrogenase	MNOD_RS02545	MNOD_RS07015
dddA	3-hydroxypropionate dehydrogenase	MNOD_RS24890	MNOD_RS17790
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	MNOD_RS19520
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	MNOD_RS21590	MNOD_RS07015
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	MNOD_RS03285	MNOD_RS25115
glcF	D-lactate dehydrogenase, FeS subunit GlcF	MNOD_RS03300
gloA	glyoxylase I	MNOD_RS25905	MNOD_RS02175
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	MNOD_RS27655	MNOD_RS02200
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	MNOD_RS00720	MNOD_RS18785
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	MNOD_RS10495	MNOD_RS12075
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	MNOD_RS30020	MNOD_RS10160
L-LDH	L-lactate dehydrogenase	MNOD_RS34990	MNOD_RS05425
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	MNOD_RS18950
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	MNOD_RS48120	MNOD_RS39190
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	MNOD_RS21590	MNOD_RS02545
lctO	L-lactate oxidase or 2-monooxygenase	MNOD_RS34990
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	MNOD_RS21545	MNOD_RS00185
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	MNOD_RS21545	MNOD_RS00185
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	MNOD_RS21545	MNOD_RS00185
pccA	propionyl-CoA carboxylase, alpha subunit	MNOD_RS09065	MNOD_RS28580
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	MNOD_RS09065	MNOD_RS28580
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	MNOD_RS28585
pccB	propionyl-CoA carboxylase, beta subunit	MNOD_RS26070	MNOD_RS01430
pco	propanyl-CoA oxidase	MNOD_RS06130
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	MNOD_RS39265	MNOD_RS07020
prpC	2-methylcitrate synthase	MNOD_RS07340
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	MNOD_RS13135
pta	phosphate acetyltransferase	MNOD_RS32625	MNOD_RS02010
serP1	L-threonine uptake transporter SerP1	MNOD_RS23565
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	MNOD_RS24820	MNOD_RS35840
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	MNOD_RS17750	MNOD_RS06795
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	MNOD_RS04665	MNOD_RS30390

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.