L-threonine catabolism in Pseudomonas taeanensis MS-3

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 (45 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)	TMS3_RS10730	TMS3_RS07890
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	TMS3_RS10725	TMS3_RS07895
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	TMS3_RS10720	TMS3_RS07900
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	TMS3_RS10715	TMS3_RS05970
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	TMS3_RS10710	TMS3_RS17915
ltaE	L-threonine aldolase	TMS3_RS00725	TMS3_RS11220
adh	acetaldehyde dehydrogenase (not acylating)	TMS3_RS20175	TMS3_RS05705
ackA	acetate kinase	TMS3_RS09795	TMS3_RS18105
pta	phosphate acetyltransferase	TMS3_RS18110	TMS3_RS09000
gcvP	glycine cleavage system, P component (glycine decarboxylase)	TMS3_RS08640	TMS3_RS04385
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	TMS3_RS08620	TMS3_RS04375
gcvH	glycine cleavage system, H component (lipoyl protein)	TMS3_RS04380	TMS3_RS08645
lpd	dihydrolipoyl dehydrogenase	TMS3_RS16525	TMS3_RS20450
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	TMS3_RS13490	TMS3_RS13040
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	TMS3_RS13490	TMS3_RS16650
acs	acetyl-CoA synthetase, AMP-forming	TMS3_RS12625	TMS3_RS07825
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	TMS3_RS08795	TMS3_RS24020
aldA	lactaldehyde dehydrogenase	TMS3_RS15350	TMS3_RS10015
D-LDH	D-lactate dehydrogenase	TMS3_RS07610	TMS3_RS01750
dddA	3-hydroxypropionate dehydrogenase	TMS3_RS08960	TMS3_RS24785
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	TMS3_RS03515	TMS3_RS07610
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	TMS3_RS03520
glcF	D-lactate dehydrogenase, FeS subunit GlcF	TMS3_RS03525
gloA	glyoxylase I	TMS3_RS14215
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	TMS3_RS12840	TMS3_RS10460
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	TMS3_RS14965	TMS3_RS19290
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	TMS3_RS06795	TMS3_RS21110
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	TMS3_RS00430	TMS3_RS19735
L-LDH	L-lactate dehydrogenase	TMS3_RS07615	TMS3_RS01630
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	TMS3_RS08875	TMS3_RS21890
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	TMS3_RS01750	TMS3_RS03515
lctO	L-lactate oxidase or 2-monooxygenase	TMS3_RS07615
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit
lutB	L-lactate dehydrogenase, LutB subunit
lutC	L-lactate dehydrogenase, LutC subunit
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	TMS3_RS21950	TMS3_RS15410
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	TMS3_RS03090	TMS3_RS06040
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	TMS3_RS15400	TMS3_RS21965
pco	propanyl-CoA oxidase	TMS3_RS02095
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	TMS3_RS13500	TMS3_RS05915
prpC	2-methylcitrate synthase	TMS3_RS13495	TMS3_RS16560
prpD	2-methylcitrate dehydratase	TMS3_RS13480
prpF	methylaconitate isomerase	TMS3_RS13485	TMS3_RS20795
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	TMS3_RS05990
sstT	L-threonine:Na+ symporter SstT	TMS3_RS11375
tdcB	L-threonine dehydratase	TMS3_RS01730	TMS3_RS03440
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	TMS3_RS24885	TMS3_RS21105
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	TMS3_RS17195	TMS3_RS14395

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.