L-threonine catabolism in Sulfuritalea hydrogenivorans DSM 22779

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 (50 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)	SUTH_RS01380
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	SUTH_RS01375	SUTH_RS00445
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	SUTH_RS01370	SUTH_RS00450
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	SUTH_RS10320	SUTH_RS00455
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	SUTH_RS06110	SUTH_RS01360
ltaE	L-threonine aldolase	SUTH_RS03505
adh	acetaldehyde dehydrogenase (not acylating)	SUTH_RS08615	SUTH_RS05840
acs	acetyl-CoA synthetase, AMP-forming	SUTH_RS11485	SUTH_RS14820
gcvP	glycine cleavage system, P component (glycine decarboxylase)	SUTH_RS05985
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	SUTH_RS05995
gcvH	glycine cleavage system, H component (lipoyl protein)	SUTH_RS05990	SUTH_RS00990
lpd	dihydrolipoyl dehydrogenase	SUTH_RS03685	SUTH_RS08985
Alternative steps:
ackA	acetate kinase	SUTH_RS02745	SUTH_RS10370
acn	(2R,3S)-2-methylcitrate dehydratase	SUTH_RS08925
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	SUTH_RS15235	SUTH_RS08615
D-LDH	D-lactate dehydrogenase	SUTH_RS03180	SUTH_RS13140
dddA	3-hydroxypropionate dehydrogenase	SUTH_RS12550	SUTH_RS13000
DVU3032	L-lactate dehydrogenase, LutC-like component	SUTH_RS15415
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	SUTH_RS15420
epi	methylmalonyl-CoA epimerase	SUTH_RS17055
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	SUTH_RS14605	SUTH_RS03180
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	SUTH_RS14600	SUTH_RS03180
glcF	D-lactate dehydrogenase, FeS subunit GlcF	SUTH_RS14595
gloA	glyoxylase I	SUTH_RS15630
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	SUTH_RS05810	SUTH_RS02325
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	SUTH_RS15075	SUTH_RS08545
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	SUTH_RS12545	SUTH_RS08615
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	SUTH_RS15845
L-LDH	L-lactate dehydrogenase	SUTH_RS14665
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	SUTH_RS14605	SUTH_RS03180
lctO	L-lactate oxidase or 2-monooxygenase	SUTH_RS14665
lldE	L-lactate dehydrogenase, LldE subunit	SUTH_RS15425
lldF	L-lactate dehydrogenase, LldF subunit	SUTH_RS15420
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	SUTH_RS15425
lutB	L-lactate dehydrogenase, LutB subunit	SUTH_RS15420
lutC	L-lactate dehydrogenase, LutC subunit	SUTH_RS15415
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	SUTH_RS17165	SUTH_RS03085
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	SUTH_RS17165
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	SUTH_RS17165	SUTH_RS03085
pccA	propionyl-CoA carboxylase, alpha subunit	SUTH_RS17150	SUTH_RS02695
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	SUTH_RS17150	SUTH_RS16605
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	SUTH_RS17155	SUTH_RS02685
pco	propanyl-CoA oxidase	SUTH_RS08235	SUTH_RS02660
phtA	L-threonine uptake permease PhtA	SUTH_RS17710
prpB	2-methylisocitrate lyase	SUTH_RS05385
prpC	2-methylcitrate synthase	SUTH_RS08970
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	SUTH_RS06145
pta	phosphate acetyltransferase	SUTH_RS10365	SUTH_RS14935
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	SUTH_RS17910
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	SUTH_RS12995	SUTH_RS14860
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 Apr 09 2024. The underlying query database was built on Sep 17 2021.