L-threonine catabolism in Neptunomonas antarctica S3-22

Best path

braC, braD, braE, braF, braG, tdh, kbl, 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 (49 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)	Nant_RS08260
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	Nant_RS08265	Nant_RS10015
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	Nant_RS08270
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	Nant_RS08275	Nant_RS10025
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	Nant_RS08280	Nant_RS10030
tdh	L-threonine 3-dehydrogenase	Nant_RS11850	Nant_RS02290
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	Nant_RS11845	Nant_RS19110
gcvP	glycine cleavage system, P component (glycine decarboxylase)	Nant_RS03050
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	Nant_RS03020	Nant_RS04745
gcvH	glycine cleavage system, H component (lipoyl protein)	Nant_RS04750	Nant_RS03045
lpd	dihydrolipoyl dehydrogenase	Nant_RS14155	Nant_RS08895
Alternative steps:
ackA	acetate kinase	Nant_RS12275	Nant_RS06470
acn	(2R,3S)-2-methylcitrate dehydratase	Nant_RS14685	Nant_RS13180
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	Nant_RS14685	Nant_RS08835
acs	acetyl-CoA synthetase, AMP-forming	Nant_RS18305	Nant_RS13480
adh	acetaldehyde dehydrogenase (not acylating)	Nant_RS14835	Nant_RS20560
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	Nant_RS17925	Nant_RS19705
D-LDH	D-lactate dehydrogenase	Nant_RS02385	Nant_RS07865
dddA	3-hydroxypropionate dehydrogenase	Nant_RS00625	Nant_RS19700
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	Nant_RS03220
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	Nant_RS07130	Nant_RS19720
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	Nant_RS07125	Nant_RS19725
glcF	D-lactate dehydrogenase, FeS subunit GlcF	Nant_RS19730	Nant_RS07120
gloA	glyoxylase I	Nant_RS09480
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	Nant_RS08760	Nant_RS07185
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	Nant_RS13960	Nant_RS07340
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	Nant_RS02295	Nant_RS18020
L-LDH	L-lactate dehydrogenase	Nant_RS15535
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	Nant_RS08080	Nant_RS00265
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	Nant_RS07865
lctO	L-lactate oxidase or 2-monooxygenase	Nant_RS15535
lldE	L-lactate dehydrogenase, LldE subunit	Nant_RS03225
lldF	L-lactate dehydrogenase, LldF subunit	Nant_RS03220
lldG	L-lactate dehydrogenase, LldG subunit
ltaE	L-threonine aldolase	Nant_RS14050	Nant_RS16475
lutA	L-lactate dehydrogenase, LutA subunit	Nant_RS03225
lutB	L-lactate dehydrogenase, LutB subunit	Nant_RS03220
lutC	L-lactate dehydrogenase, LutC subunit	Nant_RS03215
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	Nant_RS13360
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
pccA	propionyl-CoA carboxylase, alpha subunit	Nant_RS12615	Nant_RS06370
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	Nant_RS08700	Nant_RS06370
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	Nant_RS12625
pco	propanyl-CoA oxidase	Nant_RS10235
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	Nant_RS14695	Nant_RS05750
prpC	2-methylcitrate synthase	Nant_RS14690	Nant_RS14190
prpD	2-methylcitrate dehydratase	Nant_RS08820
prpF	methylaconitate isomerase	Nant_RS14680	Nant_RS05565
pta	phosphate acetyltransferase	Nant_RS06465
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	Nant_RS09175
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	Nant_RS04555	Nant_RS07915
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
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 Sep 24 2021. The underlying query database was built on Sep 17 2021.