L-threonine catabolism in Paraburkholderia atlantica CCGE1002

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 (57 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
snatA	L-threonine transporter snatA	BC1002_RS13485
ltaE	L-threonine aldolase	BC1002_RS10275	BC1002_RS17175
adh	acetaldehyde dehydrogenase (not acylating)	BC1002_RS32750	BC1002_RS18170
acs	acetyl-CoA synthetase, AMP-forming	BC1002_RS05135	BC1002_RS26145
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BC1002_RS15480
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BC1002_RS15470	BC1002_RS32780
gcvH	glycine cleavage system, H component (lipoyl protein)	BC1002_RS15475
lpd	dihydrolipoyl dehydrogenase	BC1002_RS09480	BC1002_RS05930
Alternative steps:
ackA	acetate kinase	BC1002_RS19450	BC1002_RS27470
acn	(2R,3S)-2-methylcitrate dehydratase	BC1002_RS16725	BC1002_RS30080
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BC1002_RS16725	BC1002_RS25685
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	BC1002_RS20545	BC1002_RS23450
aldA	lactaldehyde dehydrogenase	BC1002_RS30590	BC1002_RS16940
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	BC1002_RS00535	BC1002_RS15500
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BC1002_RS11925	BC1002_RS34550
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BC1002_RS29780	BC1002_RS11920
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BC1002_RS29780	BC1002_RS34540
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BC1002_RS34535	BC1002_RS29020
D-LDH	D-lactate dehydrogenase	BC1002_RS02420	BC1002_RS02755
dddA	3-hydroxypropionate dehydrogenase	BC1002_RS15655	BC1002_RS14945
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	BC1002_RS09455	BC1002_RS20050
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BC1002_RS02415	BC1002_RS02420
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BC1002_RS02410	BC1002_RS18400
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BC1002_RS02405
gloA	glyoxylase I	BC1002_RS01990	BC1002_RS21900
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BC1002_RS10490	BC1002_RS00570
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	BC1002_RS13735	BC1002_RS28515
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BC1002_RS15660	BC1002_RS20980
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BC1002_RS25315	BC1002_RS00960
L-LDH	L-lactate dehydrogenase	BC1002_RS17560	BC1002_RS30370
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	BC1002_RS33970
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BC1002_RS33965	BC1002_RS11060
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BC1002_RS02420	BC1002_RS18400
lctO	L-lactate oxidase or 2-monooxygenase	BC1002_RS27270	BC1002_RS30370
lldE	L-lactate dehydrogenase, LldE subunit	BC1002_RS20055	BC1002_RS09460
lldF	L-lactate dehydrogenase, LldF subunit	BC1002_RS20050	BC1002_RS09455
lldG	L-lactate dehydrogenase, LldG subunit	BC1002_RS20045
lutA	L-lactate dehydrogenase, LutA subunit	BC1002_RS09460	BC1002_RS20055
lutB	L-lactate dehydrogenase, LutB subunit	BC1002_RS09455	BC1002_RS20050
lutC	L-lactate dehydrogenase, LutC subunit	BC1002_RS10805
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	BC1002_RS27945	BC1002_RS00885
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BC1002_RS27945
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BC1002_RS00885	BC1002_RS27945
pccA	propionyl-CoA carboxylase, alpha subunit	BC1002_RS21425	BC1002_RS13415
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BC1002_RS13415	BC1002_RS21425
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BC1002_RS21435
pco	propanyl-CoA oxidase	BC1002_RS02685	BC1002_RS20990
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BC1002_RS08945	BC1002_RS19965
prpC	2-methylcitrate synthase	BC1002_RS25700	BC1002_RS16720
prpD	2-methylcitrate dehydratase	BC1002_RS25690
prpF	methylaconitate isomerase	BC1002_RS16730	BC1002_RS06220
pta	phosphate acetyltransferase	BC1002_RS27465	BC1002_RS13290
RR42_RS28305	L-threonine:H+ symporter	BC1002_RS11820	BC1002_RS33045
serP1	L-threonine uptake transporter SerP1	BC1002_RS11820	BC1002_RS33045
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	BC1002_RS01830	BC1002_RS08185
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BC1002_RS25320	BC1002_RS10265
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BC1002_RS29470	BC1002_RS12200

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.