L-threonine catabolism in Desulfitobacterium hafniense DCB-2

Best path

sstT, 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 (44 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
sstT	L-threonine:Na+ symporter SstT	DHAF_RS13325
ltaE	L-threonine aldolase	DHAF_RS05420	DHAF_RS24045
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	DHAF_RS24370	DHAF_RS24440
gcvP	glycine cleavage system, P component (glycine decarboxylase)	DHAF_RS20135	DHAF_RS20130
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	DHAF_RS20145
gcvH	glycine cleavage system, H component (lipoyl protein)	DHAF_RS20140
lpd	dihydrolipoyl dehydrogenase	DHAF_RS20325
Alternative steps:
ackA	acetate kinase	DHAF_RS19110	DHAF_RS17680
acn	(2R,3S)-2-methylcitrate dehydratase
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)
acs	acetyl-CoA synthetase, AMP-forming	DHAF_RS02415	DHAF_RS22940
adh	acetaldehyde dehydrogenase (not acylating)	DHAF_RS13220	DHAF_RS10840
aldA	lactaldehyde dehydrogenase	DHAF_RS13220	DHAF_RS10840
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)	DHAF_RS24540
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	DHAF_RS24530	DHAF_RS24525
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	DHAF_RS24525	DHAF_RS01145
D-LDH	D-lactate dehydrogenase	DHAF_RS16125	DHAF_RS22570
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component	DHAF_RS15375
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	DHAF_RS15370	DHAF_RS16275
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	DHAF_RS22570	DHAF_RS21890
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	DHAF_RS24335
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	DHAF_RS17985	DHAF_RS05080
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	DHAF_RS14270	DHAF_RS18210
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	DHAF_RS13220
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)
L-LDH	L-lactate dehydrogenase	DHAF_RS08965	DHAF_RS22055
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	DHAF_RS13885
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	DHAF_RS13880	DHAF_RS14295
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	DHAF_RS22570	DHAF_RS03590
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	DHAF_RS16270
lldF	L-lactate dehydrogenase, LldF subunit	DHAF_RS16275	DHAF_RS15370
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	DHAF_RS16270	DHAF_RS15370
lutB	L-lactate dehydrogenase, LutB subunit	DHAF_RS16275	DHAF_RS15370
lutC	L-lactate dehydrogenase, LutC subunit	DHAF_RS16280	DHAF_RS15375
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	DHAF_RS13500
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	DHAF_RS13505	DHAF_RS14625
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	DHAF_RS13500
pccA	propionyl-CoA carboxylase, alpha subunit	DHAF_RS17500
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	DHAF_RS17500
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit
pco	propanyl-CoA oxidase	DHAF_RS19060	DHAF_RS14305
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	DHAF_RS04540
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	DHAF_RS20120	DHAF_RS01850
RR42_RS28305	L-threonine:H+ symporter	DHAF_RS06640	DHAF_RS12190
serP1	L-threonine uptake transporter SerP1	DHAF_RS12190	DHAF_RS06640
snatA	L-threonine transporter snatA
tdcB	L-threonine dehydratase	DHAF_RS05030	DHAF_RS05410
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	DHAF_RS02645	DHAF_RS10835
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	DHAF_RS14440

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.