L-threonine catabolism in Polaromonas naphthalenivorans CJ2

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 (48 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)	PNAP_RS10865	PNAP_RS19290
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	PNAP_RS16005	PNAP_RS08255
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	PNAP_RS16000	PNAP_RS08260
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	PNAP_RS15995	PNAP_RS17570
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	PNAP_RS17565	PNAP_RS08270
ltaE	L-threonine aldolase	PNAP_RS18250	PNAP_RS14515
adh	acetaldehyde dehydrogenase (not acylating)	PNAP_RS19250	PNAP_RS15070
ackA	acetate kinase	PNAP_RS22490	PNAP_RS17810
pta	phosphate acetyltransferase	PNAP_RS22490	PNAP_RS17805
gcvP	glycine cleavage system, P component (glycine decarboxylase)	PNAP_RS13410
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	PNAP_RS13400
gcvH	glycine cleavage system, H component (lipoyl protein)	PNAP_RS13405
lpd	dihydrolipoyl dehydrogenase	PNAP_RS08930	PNAP_RS09310
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	PNAP_RS15125	PNAP_RS15140
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	PNAP_RS15125
acs	acetyl-CoA synthetase, AMP-forming	PNAP_RS14380	PNAP_RS16370
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	PNAP_RS20640
aldA	lactaldehyde dehydrogenase	PNAP_RS15070	PNAP_RS13310
D-LDH	D-lactate dehydrogenase	PNAP_RS00360	PNAP_RS13840
dddA	3-hydroxypropionate dehydrogenase	PNAP_RS00880	PNAP_RS20845
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	PNAP_RS11895
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	PNAP_RS01450	PNAP_RS00360
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	PNAP_RS00610	PNAP_RS00360
glcF	D-lactate dehydrogenase, FeS subunit GlcF	PNAP_RS00620
gloA	glyoxylase I	PNAP_RS14925	PNAP_RS17510
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	PNAP_RS08385	PNAP_RS06155
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	PNAP_RS16825	PNAP_RS10675
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	PNAP_RS18995	PNAP_RS07980
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	PNAP_RS20095
L-LDH	L-lactate dehydrogenase	PNAP_RS15765	PNAP_RS05080
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	PNAP_RS11570
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	PNAP_RS11575	PNAP_RS10695
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	PNAP_RS00360	PNAP_RS01450
lctO	L-lactate oxidase or 2-monooxygenase	PNAP_RS12795	PNAP_RS05080
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	PNAP_RS11920	PNAP_RS17595
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	PNAP_RS11920
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	PNAP_RS11920	PNAP_RS17595
pccA	propionyl-CoA carboxylase, alpha subunit	PNAP_RS11900	PNAP_RS02355
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	PNAP_RS11900	PNAP_RS16940
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	PNAP_RS02355
pccB	propionyl-CoA carboxylase, beta subunit	PNAP_RS11910	PNAP_RS02335
pco	propanyl-CoA oxidase	PNAP_RS10685	PNAP_RS05675
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	PNAP_RS14265
prpC	2-methylcitrate synthase	PNAP_RS15190
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	PNAP_RS19010	PNAP_RS10190
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	PNAP_RS00910
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	PNAP_RS03190	PNAP_RS00550
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	PNAP_RS09740	PNAP_RS10390
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.