L-threonine catabolism in Desulfobulbus mediterraneus DSM 13871

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 (51 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)	G494_RS0110185	G494_RS0112100
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	G494_RS0110180	G494_RS0119640
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	G494_RS0110175	G494_RS0119635
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	G494_RS0110170	G494_RS0119630
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	G494_RS0110165	G494_RS0106710
ltaE	L-threonine aldolase	G494_RS0105475	G494_RS0117855
adh	acetaldehyde dehydrogenase (not acylating)	G494_RS0111845	G494_RS0112240
ackA	acetate kinase	G494_RS0119820
pta	phosphate acetyltransferase	G494_RS0109915	G494_RS0105455
gcvP	glycine cleavage system, P component (glycine decarboxylase)	G494_RS0108195	G494_RS0108190
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	G494_RS0108205
gcvH	glycine cleavage system, H component (lipoyl protein)	G494_RS0108200
lpd	dihydrolipoyl dehydrogenase	G494_RS0104025	G494_RS0107595
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	G494_RS0118470	G494_RS22525
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	G494_RS0118470
acs	acetyl-CoA synthetase, AMP-forming	G494_RS0103595	G494_RS0120850
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	G494_RS0120720	G494_RS0112240
D-LDH	D-lactate dehydrogenase	G494_RS0101840	G494_RS0102495
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component	G494_RS0101990	G494_RS23915
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	G494_RS0101995	G494_RS23920
epi	methylmalonyl-CoA epimerase	G494_RS0112200	G494_RS0109355
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	G494_RS0101860	G494_RS0102495
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	G494_RS0102495	G494_RS0101860
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	G494_RS0103855	G494_RS0102855
grdA	glycine reductase component A1	G494_RS0115255
grdB	glycine reductase component B, gamma subunit	G494_RS0115265
grdC	glycine reductase component C, beta subunit	G494_RS23810
grdD	glycine reductase component C, alpha subunit
grdE	glycine reductase component B, precursor to alpha/beta subunits	G494_RS0115270
hpcD	3-hydroxypropionyl-CoA dehydratase	G494_RS0116145	G494_RS0115915
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	G494_RS0112755	G494_RS0101615
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	G494_RS0113655	G494_RS0118995
L-LDH	L-lactate dehydrogenase
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	G494_RS0109100
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	G494_RS0109095
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	G494_RS0102495	G494_RS0101860
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	G494_RS0115710
lldF	L-lactate dehydrogenase, LldF subunit	G494_RS23920	G494_RS0101995
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	G494_RS0115710	G494_RS0101995
lutB	L-lactate dehydrogenase, LutB subunit	G494_RS23920	G494_RS0101995
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	G494_RS0117545	G494_RS0109360
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	G494_RS0109360	G494_RS0117545
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	G494_RS0109360	G494_RS0117545
pccA	propionyl-CoA carboxylase, alpha subunit	G494_RS0107515
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	G494_RS0107515
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	G494_RS0114540
pccB	propionyl-CoA carboxylase, beta subunit	G494_RS0100190	G494_RS0114325
pco	propanyl-CoA oxidase	G494_RS0103780
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	G494_RS0115625
prpC	2-methylcitrate synthase	G494_RS0118500	G494_RS0115440
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
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	G494_RS0112930	G494_RS0116150
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	G494_RS0113660	G494_RS0110865
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	G494_RS24530

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.