L-threonine catabolism in Methylibium petroleiphilum PM1

Best path

snatA, 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 (44 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
snatA	L-threonine transporter snatA	MPE_RS19200
ltaE	L-threonine aldolase	MPE_RS07215	MPE_RS16470
adh	acetaldehyde dehydrogenase (not acylating)	MPE_RS10400	MPE_RS03015
acs	acetyl-CoA synthetase, AMP-forming	MPE_RS06980	MPE_RS01740
gcvP	glycine cleavage system, P component (glycine decarboxylase)	MPE_RS07220
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	MPE_RS07230
gcvH	glycine cleavage system, H component (lipoyl protein)	MPE_RS07225
lpd	dihydrolipoyl dehydrogenase	MPE_RS10715	MPE_RS10145
Alternative steps:
ackA	acetate kinase
acn	(2R,3S)-2-methylcitrate dehydratase	MPE_RS06870	MPE_RS06845
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	MPE_RS06845
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	MPE_RS11440	MPE_RS16770
aldA	lactaldehyde dehydrogenase	MPE_RS01830	MPE_RS03015
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	MPE_RS09770
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	MPE_RS05630	MPE_RS18565
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	MPE_RS05635
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	MPE_RS05640	MPE_RS18955
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	MPE_RS05645	MPE_RS18575
D-LDH	D-lactate dehydrogenase	MPE_RS19055	MPE_RS07165
dddA	3-hydroxypropionate dehydrogenase	MPE_RS19195
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	MPE_RS05085
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	MPE_RS18380	MPE_RS04790
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	MPE_RS18385	MPE_RS04795
glcF	D-lactate dehydrogenase, FeS subunit GlcF	MPE_RS18390	MPE_RS04800
gloA	glyoxylase I	MPE_RS18275	MPE_RS14755
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	MPE_RS12755	MPE_RS04665
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	MPE_RS03005	MPE_RS04395
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	MPE_RS17810	MPE_RS09615
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	MPE_RS02665
L-LDH	L-lactate dehydrogenase	MPE_RS14270	MPE_RS01825
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	MPE_RS06535
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	MPE_RS19055	MPE_RS18380
lctO	L-lactate oxidase or 2-monooxygenase	MPE_RS01825	MPE_RS14270
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	MPE_RS05065	MPE_RS22140
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	MPE_RS05065	MPE_RS22125
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	MPE_RS05065	MPE_RS04505
pccA	propionyl-CoA carboxylase, alpha subunit	MPE_RS05080	MPE_RS16940
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	MPE_RS05080	MPE_RS16190
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	MPE_RS05075	MPE_RS16955
pco	propanyl-CoA oxidase	MPE_RS16000
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	MPE_RS09515
prpC	2-methylcitrate synthase	MPE_RS10925
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	MPE_RS01025
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	MPE_RS15770	MPE_RS19035
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	MPE_RS09055	MPE_RS18480
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)

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.