L-threonine catabolism in Pseudomonas simiae WCS417

Best path

braC, braD, braE, braF, braG, ltaE, adh, ackA, pta, gcvP, gcvT, gcvH, lpd

Also see fitness data for the top candidates

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 (43 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)	PS417_06615	PS417_02655
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	PS417_06610	PS417_02660
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	PS417_06605	PS417_02665
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	PS417_06600	PS417_17675
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	PS417_06595	PS417_02675
ltaE	L-threonine aldolase	PS417_26205	PS417_21665
adh	acetaldehyde dehydrogenase (not acylating)	PS417_17430	PS417_24810
ackA	acetate kinase	PS417_22945
pta	phosphate acetyltransferase	PS417_03730
gcvP	glycine cleavage system, P component (glycine decarboxylase)	PS417_22360
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	PS417_22370	PS417_27255
gcvH	glycine cleavage system, H component (lipoyl protein)	PS417_27250	PS417_22355
lpd	dihydrolipoyl dehydrogenase	PS417_17560	PS417_08905
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	PS417_21070	PS417_14990
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	PS417_21070	PS417_07515
acs	acetyl-CoA synthetase, AMP-forming	PS417_21750	PS417_23925
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	PS417_17430	PS417_24810
D-LDH	D-lactate dehydrogenase	PS417_24110	PS417_16375
dddA	3-hydroxypropionate dehydrogenase	PS417_10560	PS417_26345
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)
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	PS417_14035
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	PS417_12220	PS417_06335
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	PS417_13845	PS417_10680
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	PS417_10925	PS417_03250
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	PS417_26000	PS417_06915
L-LDH	L-lactate dehydrogenase	PS417_19130	PS417_15625
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	PS417_21295
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component
lctO	L-lactate oxidase or 2-monooxygenase	PS417_15625	PS417_19130
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	PS417_19595	PS417_17030
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	PS417_28215	PS417_02965
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	PS417_17020	PS417_19580
pco	propanyl-CoA oxidase	PS417_00580	PS417_13850
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	PS417_21080	PS417_16570
prpC	2-methylcitrate synthase	PS417_21075	PS417_08870
prpD	2-methylcitrate dehydratase	PS417_21060
prpF	methylaconitate isomerase	PS417_21065	PS417_07225
RR42_RS28305	L-threonine:H+ symporter	PS417_05405	PS417_01755
serP1	L-threonine uptake transporter SerP1	PS417_14545	PS417_23700
snatA	L-threonine transporter snatA	PS417_02925
sstT	L-threonine:Na+ symporter SstT	PS417_10435
tdcB	L-threonine dehydratase	PS417_27010	PS417_12665
tdcC	L-threonine:H+ symporter TdcC	PS417_14995	PS417_05070
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	PS417_06905	PS417_25740
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	PS417_10670	PS417_15340

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 17 2021. The underlying query database was built on Sep 17 2021.