L-threonine catabolism in Lutibaculum baratangense AMV1

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 (50 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)	N177_RS20180	N177_RS02905
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	N177_RS20205	N177_RS02910
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	N177_RS20200	N177_RS02915
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	N177_RS20195	N177_RS07365
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	N177_RS20190	N177_RS07360
ltaE	L-threonine aldolase	N177_RS13060	N177_RS16095
adh	acetaldehyde dehydrogenase (not acylating)	N177_RS19425	N177_RS12830
acs	acetyl-CoA synthetase, AMP-forming	N177_RS17855	N177_RS08505
gcvP	glycine cleavage system, P component (glycine decarboxylase)	N177_RS05320	N177_RS05325
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	N177_RS05340	N177_RS11500
gcvH	glycine cleavage system, H component (lipoyl protein)	N177_RS05335
lpd	dihydrolipoyl dehydrogenase	N177_RS17285	N177_RS12135
Alternative steps:
ackA	acetate kinase
acn	(2R,3S)-2-methylcitrate dehydratase	N177_RS06340	N177_RS14365
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	N177_RS06340	N177_RS14365
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	N177_RS08305	N177_RS14415
D-LDH	D-lactate dehydrogenase	N177_RS01470	N177_RS13375
dddA	3-hydroxypropionate dehydrogenase	N177_RS10510	N177_RS18905
DVU3032	L-lactate dehydrogenase, LutC-like component	N177_RS08090
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	N177_RS08085
epi	methylmalonyl-CoA epimerase	N177_RS09745
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	N177_RS04320	N177_RS01470
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	N177_RS04325
glcF	D-lactate dehydrogenase, FeS subunit GlcF	N177_RS04330
gloA	glyoxylase I	N177_RS16395	N177_RS13485
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	N177_RS12105	N177_RS15755
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	N177_RS05770	N177_RS14645
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	N177_RS13385	N177_RS12830
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	N177_RS14250
L-LDH	L-lactate dehydrogenase	N177_RS12160	N177_RS14335
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	N177_RS04320	N177_RS10090
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	N177_RS08080
lldF	L-lactate dehydrogenase, LldF subunit	N177_RS08085
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	N177_RS08080
lutB	L-lactate dehydrogenase, LutB subunit	N177_RS08085
lutC	L-lactate dehydrogenase, LutC subunit	N177_RS08090
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	N177_RS18710
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	N177_RS18710	N177_RS01680
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	N177_RS18710
pccA	propionyl-CoA carboxylase, alpha subunit	N177_RS03830	N177_RS14790
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	N177_RS03830	N177_RS09475
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	N177_RS03810	N177_RS14785
pco	propanyl-CoA oxidase	N177_RS18745
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	N177_RS02110
prpC	2-methylcitrate synthase	N177_RS17135
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	N177_RS07935	N177_RS18080
pta	phosphate acetyltransferase	N177_RS06645	N177_RS17335
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	N177_RS21150
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	N177_RS16030	N177_RS12980
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	N177_RS04155	N177_RS00865
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	N177_RS03885	N177_RS03345

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.