L-threonine catabolism in Novosphingobium barchaimii LL02

Best path

snatA, ltaE, adh, acs, 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 (37 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
snatA	L-threonine transporter snatA	V474_RS07020
ltaE	L-threonine aldolase	V474_RS14035	V474_RS04295
adh	acetaldehyde dehydrogenase (not acylating)	V474_RS12520	V474_RS17175
acs	acetyl-CoA synthetase, AMP-forming	V474_RS03815	V474_RS05855
gcvP	glycine cleavage system, P component (glycine decarboxylase)	V474_RS04460	V474_RS04455
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	V474_RS04470
gcvH	glycine cleavage system, H component (lipoyl protein)	V474_RS04465
lpd	dihydrolipoyl dehydrogenase	V474_RS03825	V474_RS11040
Alternative steps:
ackA	acetate kinase
acn	(2R,3S)-2-methylcitrate dehydratase	V474_RS13470	V474_RS08450
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	V474_RS13470	V474_RS10030
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	V474_RS01290
aldA	lactaldehyde dehydrogenase	V474_RS10060	V474_RS12520
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)
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)	V474_RS15730	V474_RS07795
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	V474_RS15730	V474_RS07795
D-LDH	D-lactate dehydrogenase	V474_RS01110	V474_RS05805
dddA	3-hydroxypropionate dehydrogenase	V474_RS12195	V474_RS23920
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	V474_RS05385
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
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	V474_RS02830	V474_RS06535
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	V474_RS01310	V474_RS16345
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	V474_RS10060	V474_RS17175
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	V474_RS13200	V474_RS05480
L-LDH	L-lactate dehydrogenase	V474_RS11020	V474_RS10765
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	V474_RS18190	V474_RS20245
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	V474_RS05805
lctO	L-lactate oxidase or 2-monooxygenase	V474_RS10765
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	V474_RS05380
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	V474_RS05380
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	V474_RS05380
pccA	propionyl-CoA carboxylase, alpha subunit	V474_RS05365	V474_RS18360
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	V474_RS05365	V474_RS22420
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	V474_RS05395	V474_RS18370
pco	propanyl-CoA oxidase
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	V474_RS10075	V474_RS09690
prpC	2-methylcitrate synthase	V474_RS03125
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	V474_RS09055
pta	phosphate acetyltransferase	V474_RS10845	V474_RS17875
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	V474_RS13280	V474_RS05525
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	V474_RS19960	V474_RS02570
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.