L-threonine catabolism in Rhodospirillum centenum SW SW; ATCC 51521

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 (52 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)	RC1_RS04995	RC1_RS05000
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	RC1_RS08780
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	RC1_RS08785
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	RC1_RS08790	RC1_RS08795
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	RC1_RS08795	RC1_RS15325
ltaE	L-threonine aldolase	RC1_RS08280	RC1_RS06420
adh	acetaldehyde dehydrogenase (not acylating)	RC1_RS06490	RC1_RS07630
acs	acetyl-CoA synthetase, AMP-forming	RC1_RS11200	RC1_RS14480
gcvP	glycine cleavage system, P component (glycine decarboxylase)	RC1_RS17505	RC1_RS17500
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	RC1_RS17490
gcvH	glycine cleavage system, H component (lipoyl protein)	RC1_RS17495
lpd	dihydrolipoyl dehydrogenase	RC1_RS00535	RC1_RS10845
Alternative steps:
ackA	acetate kinase	RC1_RS19480
acn	(2R,3S)-2-methylcitrate dehydratase	RC1_RS16110
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	RC1_RS16110
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	RC1_RS06940	RC1_RS07630
D-LDH	D-lactate dehydrogenase	RC1_RS07805	RC1_RS10335
dddA	3-hydroxypropionate dehydrogenase	RC1_RS07605
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	RC1_RS13765
epi	methylmalonyl-CoA epimerase	RC1_RS05840
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	RC1_RS10335	RC1_RS07805
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	RC1_RS10330
glcF	D-lactate dehydrogenase, FeS subunit GlcF	RC1_RS10320	RC1_RS13760
gloA	glyoxylase I	RC1_RS02815
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	RC1_RS16430	RC1_RS11885
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	RC1_RS14595	RC1_RS04605
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	RC1_RS07630	RC1_RS06940
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	RC1_RS04725	RC1_RS10110
L-LDH	L-lactate dehydrogenase	RC1_RS16775	RC1_RS19520
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	RC1_RS17675
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	RC1_RS17680	RC1_RS19650
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	RC1_RS10335	RC1_RS07805
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	RC1_RS13760
lldF	L-lactate dehydrogenase, LldF subunit	RC1_RS13765
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	RC1_RS13760
lutB	L-lactate dehydrogenase, LutB subunit	RC1_RS13765
lutC	L-lactate dehydrogenase, LutC subunit	RC1_RS13770
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	RC1_RS14910
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	RC1_RS14910
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	RC1_RS14910
pccA	propionyl-CoA carboxylase, alpha subunit	RC1_RS01950	RC1_RS01795
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	RC1_RS01950	RC1_RS04410
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	RC1_RS01795
pccB	propionyl-CoA carboxylase, beta subunit	RC1_RS01980	RC1_RS01840
pco	propanyl-CoA oxidase	RC1_RS00640
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	RC1_RS12880	RC1_RS18195
prpC	2-methylcitrate synthase	RC1_RS18200	RC1_RS05690
prpD	2-methylcitrate dehydratase	RC1_RS18205
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	RC1_RS01915	RC1_RS15600
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	RC1_RS12005	RC1_RS15810
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	RC1_RS15150	RC1_RS03695
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	RC1_RS12710
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)

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.