L-threonine catabolism in Nocardiopsis gilva YIM 90087

Best path

RR42_RS28305, 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 (51 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
RR42_RS28305	L-threonine:H+ symporter	CDO52_RS05495	CDO52_RS15070
ltaE	L-threonine aldolase	CDO52_RS09105	CDO52_RS08380
adh	acetaldehyde dehydrogenase (not acylating)	CDO52_RS12255	CDO52_RS21175
ackA	acetate kinase	CDO52_RS09405
pta	phosphate acetyltransferase	CDO52_RS09400
gcvP	glycine cleavage system, P component (glycine decarboxylase)	CDO52_RS13635
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	CDO52_RS08390	CDO52_RS10670
gcvH	glycine cleavage system, H component (lipoyl protein)	CDO52_RS08385
lpd	dihydrolipoyl dehydrogenase	CDO52_RS03320	CDO52_RS11375
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	CDO52_RS18190
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	CDO52_RS18190
acs	acetyl-CoA synthetase, AMP-forming	CDO52_RS03110	CDO52_RS08400
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	CDO52_RS21175	CDO52_RS14780
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)	CDO52_RS12545
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	CDO52_RS12550
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	CDO52_RS12555	CDO52_RS12560
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	CDO52_RS12560	CDO52_RS18110
D-LDH	D-lactate dehydrogenase	CDO52_RS20985	CDO52_RS09920
dddA	3-hydroxypropionate dehydrogenase	CDO52_RS07215
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	CDO52_RS14025
epi	methylmalonyl-CoA epimerase	CDO52_RS23050
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	CDO52_RS09920	CDO52_RS20035
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	CDO52_RS09915
glcF	D-lactate dehydrogenase, FeS subunit GlcF	CDO52_RS09910
gloA	glyoxylase I	CDO52_RS16775
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	CDO52_RS19250	CDO52_RS24495
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	CDO52_RS22645	CDO52_RS01700
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	CDO52_RS09015	CDO52_RS05450
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	CDO52_RS17855	CDO52_RS03755
L-LDH	L-lactate dehydrogenase	CDO52_RS13310
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	CDO52_RS22630
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	CDO52_RS09920
lctO	L-lactate oxidase or 2-monooxygenase	CDO52_RS13310
lldE	L-lactate dehydrogenase, LldE subunit	CDO52_RS14030
lldF	L-lactate dehydrogenase, LldF subunit	CDO52_RS14025
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	CDO52_RS14030
lutB	L-lactate dehydrogenase, LutB subunit	CDO52_RS14025
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	CDO52_RS04240	CDO52_RS23020
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	CDO52_RS24735	CDO52_RS04240
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	CDO52_RS04240	CDO52_RS23020
pccA	propionyl-CoA carboxylase, alpha subunit	CDO52_RS24535	CDO52_RS21065
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	CDO52_RS24535	CDO52_RS21065
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	CDO52_RS10880
pccB	propionyl-CoA carboxylase, beta subunit	CDO52_RS24525	CDO52_RS10885
pco	propanyl-CoA oxidase	CDO52_RS21045	CDO52_RS01715
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	CDO52_RS13490
prpC	2-methylcitrate synthase	CDO52_RS26575	CDO52_RS05220
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
serP1	L-threonine uptake transporter SerP1	CDO52_RS05495
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	CDO52_RS17305	CDO52_RS14725
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	CDO52_RS17250	CDO52_RS24500
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	CDO52_RS13220

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.