L-threonine catabolism in Marivita geojedonensis DPG-138

Best path

braC, braD, braE, braF, braG, 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 (46 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)	MGEO_RS14450
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	MGEO_RS14465	MGEO_RS19850
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	MGEO_RS14470	MGEO_RS19845
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	MGEO_RS19860	MGEO_RS14455
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	MGEO_RS14460	MGEO_RS19855
ltaE	L-threonine aldolase	MGEO_RS04160	MGEO_RS16680
adh	acetaldehyde dehydrogenase (not acylating)	MGEO_RS02095	MGEO_RS02570
acs	acetyl-CoA synthetase, AMP-forming	MGEO_RS21005	MGEO_RS10460
gcvP	glycine cleavage system, P component (glycine decarboxylase)	MGEO_RS16605
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	MGEO_RS16615	MGEO_RS09725
gcvH	glycine cleavage system, H component (lipoyl protein)	MGEO_RS16610
lpd	dihydrolipoyl dehydrogenase	MGEO_RS09565	MGEO_RS18755
Alternative steps:
ackA	acetate kinase	MGEO_RS02500
acn	(2R,3S)-2-methylcitrate dehydratase	MGEO_RS14690
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	MGEO_RS14690
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	MGEO_RS07470	MGEO_RS02095
D-LDH	D-lactate dehydrogenase	MGEO_RS08420	MGEO_RS06960
dddA	3-hydroxypropionate dehydrogenase	MGEO_RS07505	MGEO_RS02655
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	MGEO_RS18700
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	MGEO_RS02315	MGEO_RS08420
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	MGEO_RS02320
glcF	D-lactate dehydrogenase, FeS subunit GlcF	MGEO_RS02325
gloA	glyoxylase I	MGEO_RS09920
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	MGEO_RS10060	MGEO_RS01450
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	MGEO_RS17480	MGEO_RS00470
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	MGEO_RS13860	MGEO_RS17260
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	MGEO_RS17650	MGEO_RS06180
L-LDH	L-lactate dehydrogenase	MGEO_RS07910	MGEO_RS00265
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	MGEO_RS18025
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	MGEO_RS08420	MGEO_RS02315
lctO	L-lactate oxidase or 2-monooxygenase	MGEO_RS07910	MGEO_RS05345
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	MGEO_RS05505	MGEO_RS00155
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	MGEO_RS05505	MGEO_RS00155
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	MGEO_RS05505	MGEO_RS00155
pccA	propionyl-CoA carboxylase, alpha subunit	MGEO_RS05495	MGEO_RS05760
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	MGEO_RS05495	MGEO_RS14815
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	MGEO_RS05475	MGEO_RS05755
pco	propanyl-CoA oxidase	MGEO_RS11945
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	MGEO_RS11935
prpC	2-methylcitrate synthase	MGEO_RS02490	MGEO_RS11295
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	MGEO_RS06775
pta	phosphate acetyltransferase	MGEO_RS02495
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	MGEO_RS06320
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	MGEO_RS12755	MGEO_RS01815
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	MGEO_RS02630	MGEO_RS05355
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	MGEO_RS06720

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.