L-threonine catabolism in Desulfacinum infernum DSM 9756

Best path

braC, braD, braE, braF, braG, ltaE, ald-dh-CoA, 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 (47 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)	BUB04_RS13175	BUB04_RS02680
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BUB04_RS13180	BUB04_RS02685
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BUB04_RS13185	BUB04_RS12270
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BUB04_RS02695	BUB04_RS13190
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BUB04_RS02700	BUB04_RS14475
ltaE	L-threonine aldolase	BUB04_RS17520	BUB04_RS18410
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	BUB04_RS17530
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BUB04_RS03940	BUB04_RS03935
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BUB04_RS03950	BUB04_RS16585
gcvH	glycine cleavage system, H component (lipoyl protein)	BUB04_RS03945	BUB04_RS06670
lpd	dihydrolipoyl dehydrogenase	BUB04_RS03960	BUB04_RS01350
Alternative steps:
ackA	acetate kinase	BUB04_RS16485	BUB04_RS17570
acn	(2R,3S)-2-methylcitrate dehydratase	BUB04_RS02125
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BUB04_RS02125
acs	acetyl-CoA synthetase, AMP-forming	BUB04_RS16450	BUB04_RS12655
adh	acetaldehyde dehydrogenase (not acylating)	BUB04_RS17530	BUB04_RS04110
aldA	lactaldehyde dehydrogenase	BUB04_RS04110	BUB04_RS05780
D-LDH	D-lactate dehydrogenase	BUB04_RS15385	BUB04_RS07455
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component	BUB04_RS07475
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	BUB04_RS07480	BUB04_RS07450
epi	methylmalonyl-CoA epimerase	BUB04_RS00980
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BUB04_RS15385	BUB04_RS07455
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BUB04_RS03445	BUB04_RS15385
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BUB04_RS07480
gloA	glyoxylase I
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BUB04_RS00890	BUB04_RS05605
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	BUB04_RS03725	BUB04_RS07705
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BUB04_RS04110	BUB04_RS13170
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)
L-LDH	L-lactate dehydrogenase	BUB04_RS00940
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	BUB04_RS12140	BUB04_RS12090
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BUB04_RS12145	BUB04_RS12085
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BUB04_RS07455	BUB04_RS15385
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	BUB04_RS07480	BUB04_RS07450
lldF	L-lactate dehydrogenase, LldF subunit	BUB04_RS07480
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	BUB04_RS07480	BUB04_RS07450
lutB	L-lactate dehydrogenase, LutB subunit	BUB04_RS07480
lutC	L-lactate dehydrogenase, LutC subunit	BUB04_RS07475
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	BUB04_RS00960	BUB04_RS13745
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BUB04_RS00965	BUB04_RS13740
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BUB04_RS00960	BUB04_RS13745
pccA	propionyl-CoA carboxylase, alpha subunit	BUB04_RS08790
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BUB04_RS08790
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BUB04_RS05245	BUB04_RS02735
pco	propanyl-CoA oxidase	BUB04_RS12135
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	BUB04_RS10620
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	BUB04_RS17565
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	BUB04_RS01900	BUB04_RS13615
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BUB04_RS10050	BUB04_RS15270
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.