L-threonine catabolism in Pontibacillus litoralis JSM 072002

Best path

tdcC, tdcB, tdcE, prpC, prpD, acn, prpB

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 (49 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
tdcC	L-threonine:H+ symporter TdcC
tdcB	L-threonine dehydratase	N784_RS07785
tdcE	2-ketobutyrate formate-lyase	N784_RS14060
prpC	2-methylcitrate synthase	N784_RS06835	N784_RS01800
prpD	2-methylcitrate dehydratase	N784_RS06830
acn	(2R,3S)-2-methylcitrate dehydratase	N784_RS06120
prpB	2-methylisocitrate lyase	N784_RS07700	N784_RS06825
Alternative steps:
ackA	acetate kinase	N784_RS01950	N784_RS05450
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	N784_RS06120
acs	acetyl-CoA synthetase, AMP-forming	N784_RS11885	N784_RS05950
adh	acetaldehyde dehydrogenase (not acylating)	N784_RS05800	N784_RS01660
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	N784_RS15060	N784_RS11410
aldA	lactaldehyde dehydrogenase	N784_RS08150	N784_RS03980
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	N784_RS05545
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	N784_RS05555	N784_RS11605
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	N784_RS05550	N784_RS06065
D-LDH	D-lactate dehydrogenase	N784_RS07755	N784_RS14115
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	N784_RS12310
epi	methylmalonyl-CoA epimerase	N784_RS07955	N784_RS11140
gcvH	glycine cleavage system, H component (lipoyl protein)	N784_RS11635
gcvP	glycine cleavage system, P component (glycine decarboxylase)	N784_RS00470	N784_RS00475
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	N784_RS00480
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	N784_RS07755
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	N784_RS07755
glcF	D-lactate dehydrogenase, FeS subunit GlcF	N784_RS07760
gloA	glyoxylase I	N784_RS10640
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	N784_RS00545
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	N784_RS08160	N784_RS01575
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	N784_RS08305	N784_RS03980
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	N784_RS02370
L-LDH	L-lactate dehydrogenase	N784_RS00595	N784_RS01790
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	N784_RS01565
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	N784_RS07755
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	N784_RS12315
lldF	L-lactate dehydrogenase, LldF subunit	N784_RS12310
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	N784_RS00075	N784_RS00255
ltaE	L-threonine aldolase	N784_RS09475
lutA	L-lactate dehydrogenase, LutA subunit	N784_RS12315	N784_RS07760
lutB	L-lactate dehydrogenase, LutB subunit	N784_RS12310
lutC	L-lactate dehydrogenase, LutC subunit	N784_RS12305
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	N784_RS07960	N784_RS09590
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	N784_RS07955
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	N784_RS09590	N784_RS07960
pccA	propionyl-CoA carboxylase, alpha subunit	N784_RS00365	N784_RS06000
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	N784_RS00365	N784_RS06000
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	N784_RS07950	N784_RS05980
pco	propanyl-CoA oxidase	N784_RS09610	N784_RS08285
phtA	L-threonine uptake permease PhtA
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	N784_RS09685	N784_RS15075
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdh	L-threonine 3-dehydrogenase	N784_RS02375	N784_RS15010
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	N784_RS12275	N784_RS06620

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.