L-threonine catabolism in Geobacter lovleyi SZ

Best path

tdcC, 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 (42 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
tdcC	L-threonine:H+ symporter TdcC
ltaE	L-threonine aldolase	GLOV_RS16495	GLOV_RS09605
adh	acetaldehyde dehydrogenase (not acylating)	GLOV_RS08400	GLOV_RS13735
ackA	acetate kinase	GLOV_RS08705	GLOV_RS02085
pta	phosphate acetyltransferase	GLOV_RS05950	GLOV_RS06215
gcvP	glycine cleavage system, P component (glycine decarboxylase)	GLOV_RS13230	GLOV_RS13225
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	GLOV_RS13245
gcvH	glycine cleavage system, H component (lipoyl protein)	GLOV_RS07905	GLOV_RS13235
lpd	dihydrolipoyl dehydrogenase	GLOV_RS07965	GLOV_RS09845
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	GLOV_RS09360
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)
acs	acetyl-CoA synthetase, AMP-forming	GLOV_RS16915	GLOV_RS06850
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	GLOV_RS14220
aldA	lactaldehyde dehydrogenase	GLOV_RS13735	GLOV_RS08400
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)	GLOV_RS09230
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	GLOV_RS09235
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	GLOV_RS09240	GLOV_RS10740
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	GLOV_RS09245	GLOV_RS10740
D-LDH	D-lactate dehydrogenase	GLOV_RS02235	GLOV_RS10345
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	GLOV_RS16155
epi	methylmalonyl-CoA epimerase	GLOV_RS16125
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	GLOV_RS02235
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	GLOV_RS02235
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	GLOV_RS16540	GLOV_RS08620
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	GLOV_RS14360
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	GLOV_RS13735	GLOV_RS08400
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	GLOV_RS08250	GLOV_RS07610
L-LDH	L-lactate dehydrogenase	GLOV_RS08065	GLOV_RS17535
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	GLOV_RS02775
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	GLOV_RS02770
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	GLOV_RS02235
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	GLOV_RS16155
lutB	L-lactate dehydrogenase, LutB subunit
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	GLOV_RS16135
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	GLOV_RS16135
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	GLOV_RS16135
pccA	propionyl-CoA carboxylase, alpha subunit	GLOV_RS07900	GLOV_RS12625
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	GLOV_RS07900	GLOV_RS12625
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	GLOV_RS16140
pccB	propionyl-CoA carboxylase, beta subunit	GLOV_RS09005	GLOV_RS16145
pco	propanyl-CoA oxidase	GLOV_RS01695
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	GLOV_RS06800
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	GLOV_RS02320
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	GLOV_RS02245	GLOV_RS00850
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	GLOV_RS07105

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.