L-threonine catabolism in Lentibacillus jeotgali Grbi

Best path

tdcC, tdh, kbl, 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 (48 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	ON01_RS13035	ON01_RS14500
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	ON01_RS13030
gcvP	glycine cleavage system, P component (glycine decarboxylase)	ON01_RS10350	ON01_RS10355
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	ON01_RS10360
gcvH	glycine cleavage system, H component (lipoyl protein)	ON01_RS16920	ON01_RS02890
lpd	dihydrolipoyl dehydrogenase	ON01_RS07445	ON01_RS10020
Alternative steps:
ackA	acetate kinase	ON01_RS17850
acn	(2R,3S)-2-methylcitrate dehydratase	ON01_RS09105
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	ON01_RS09105
acs	acetyl-CoA synthetase, AMP-forming	ON01_RS11790	ON01_RS03745
adh	acetaldehyde dehydrogenase (not acylating)	ON01_RS16395	ON01_RS16145
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	ON01_RS12160	ON01_RS04100
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	ON01_RS16055	ON01_RS03290
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	ON01_RS00395	ON01_RS02030
D-LDH	D-lactate dehydrogenase	ON01_RS04195	ON01_RS13845
dddA	3-hydroxypropionate dehydrogenase	ON01_RS06640
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	ON01_RS12090
epi	methylmalonyl-CoA epimerase	ON01_RS09990
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	ON01_RS13845	ON01_RS04195
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	ON01_RS13835
glcF	D-lactate dehydrogenase, FeS subunit GlcF	ON01_RS13840
gloA	glyoxylase I	ON01_RS04380	ON01_RS02050
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	ON01_RS10425	ON01_RS01835
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	ON01_RS06105	ON01_RS18180
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	ON01_RS15275	ON01_RS03650
L-LDH	L-lactate dehydrogenase	ON01_RS14485	ON01_RS17985
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	ON01_RS06170	ON01_RS18190
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	ON01_RS13845	ON01_RS04195
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	ON01_RS12085
lldF	L-lactate dehydrogenase, LldF subunit	ON01_RS12090
lldG	L-lactate dehydrogenase, LldG subunit
ltaE	L-threonine aldolase	ON01_RS13415
lutA	L-lactate dehydrogenase, LutA subunit	ON01_RS12085
lutB	L-lactate dehydrogenase, LutB subunit	ON01_RS12090
lutC	L-lactate dehydrogenase, LutC subunit	ON01_RS12095
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	ON01_RS13315
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	ON01_RS09990
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	ON01_RS13315
pccA	propionyl-CoA carboxylase, alpha subunit	ON01_RS10240	ON01_RS09190
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	ON01_RS10240	ON01_RS09190
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	ON01_RS09985	ON01_RS09205
pco	propanyl-CoA oxidase	ON01_RS13295	ON01_RS13300
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	ON01_RS16810	ON01_RS15070
prpC	2-methylcitrate synthase	ON01_RS15060	ON01_RS17975
prpD	2-methylcitrate dehydratase	ON01_RS15065
prpF	methylaconitate isomerase	ON01_RS01060	ON01_RS14775
pta	phosphate acetyltransferase	ON01_RS13225
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	ON01_RS15985	ON01_RS16160
tdcE	2-ketobutyrate formate-lyase
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	ON01_RS16180	ON01_RS01815

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.