L-threonine catabolism in Pseudomonas benzenivorans DSM 8628

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 (49 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)	BLS63_RS09655	BLS63_RS23775
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BLS63_RS09650	BLS63_RS23780
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BLS63_RS09645	BLS63_RS23785
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BLS63_RS09640	BLS63_RS23790
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BLS63_RS09635	BLS63_RS23795
ltaE	L-threonine aldolase	BLS63_RS26060	BLS63_RS04015
adh	acetaldehyde dehydrogenase (not acylating)	BLS63_RS17270	BLS63_RS19270
ackA	acetate kinase	BLS63_RS09000	BLS63_RS21520
pta	phosphate acetyltransferase	BLS63_RS21525
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BLS63_RS24800	BLS63_RS11160
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BLS63_RS24785	BLS63_RS11170
gcvH	glycine cleavage system, H component (lipoyl protein)	BLS63_RS11165	BLS63_RS24805
lpd	dihydrolipoyl dehydrogenase	BLS63_RS00200	BLS63_RS25065
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	BLS63_RS00675	BLS63_RS00850
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BLS63_RS00675	BLS63_RS00030
acs	acetyl-CoA synthetase, AMP-forming	BLS63_RS26090	BLS63_RS23690
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	BLS63_RS02455	BLS63_RS17010
aldA	lactaldehyde dehydrogenase	BLS63_RS22155	BLS63_RS03170
D-LDH	D-lactate dehydrogenase	BLS63_RS14300	BLS63_RS16595
dddA	3-hydroxypropionate dehydrogenase	BLS63_RS09135	BLS63_RS14560
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	BLS63_RS14310
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BLS63_RS18815	BLS63_RS10140
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BLS63_RS18820	BLS63_RS10140
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BLS63_RS18825
gloA	glyoxylase I	BLS63_RS23180	BLS63_RS17660
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BLS63_RS09480	BLS63_RS01065
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	BLS63_RS06660	BLS63_RS21705
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BLS63_RS14055	BLS63_RS21720
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BLS63_RS04165
L-LDH	L-lactate dehydrogenase
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BLS63_RS18395
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BLS63_RS18815	BLS63_RS16595
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	BLS63_RS14315
lldF	L-lactate dehydrogenase, LldF subunit	BLS63_RS14310
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	BLS63_RS14315
lutB	L-lactate dehydrogenase, LutB subunit	BLS63_RS14310
lutC	L-lactate dehydrogenase, LutC subunit	BLS63_RS14305
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
pccA	propionyl-CoA carboxylase, alpha subunit	BLS63_RS18330	BLS63_RS24345
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BLS63_RS15655	BLS63_RS04465
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BLS63_RS24335	BLS63_RS18315
pco	propanyl-CoA oxidase	BLS63_RS14585
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BLS63_RS00665	BLS63_RS21130
prpC	2-methylcitrate synthase	BLS63_RS00670	BLS63_RS00165
prpD	2-methylcitrate dehydratase	BLS63_RS00685
prpF	methylaconitate isomerase	BLS63_RS00680	BLS63_RS13860
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	BLS63_RS04515
sstT	L-threonine:Na+ symporter SstT	BLS63_RS19390
tdcB	L-threonine dehydratase	BLS63_RS16565
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BLS63_RS17235	BLS63_RS10745
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BLS63_RS12250	BLS63_RS22095

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.