L-threonine catabolism in Duganella sacchari Sac-22

Best path

RR42_RS28305, 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 (48 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
RR42_RS28305	L-threonine:H+ symporter	BUA36_RS06065	BUA36_RS24700
ltaE	L-threonine aldolase	BUA36_RS01325	BUA36_RS16260
adh	acetaldehyde dehydrogenase (not acylating)	BUA36_RS13005	BUA36_RS02795
acs	acetyl-CoA synthetase, AMP-forming	BUA36_RS11840	BUA36_RS28615
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BUA36_RS11125	BUA36_RS17885
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BUA36_RS11135
gcvH	glycine cleavage system, H component (lipoyl protein)	BUA36_RS11130
lpd	dihydrolipoyl dehydrogenase	BUA36_RS22760	BUA36_RS01790
Alternative steps:
ackA	acetate kinase	BUA36_RS04825	BUA36_RS05735
acn	(2R,3S)-2-methylcitrate dehydratase	BUA36_RS28625	BUA36_RS06375
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BUA36_RS28625	BUA36_RS01905
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	BUA36_RS24730
aldA	lactaldehyde dehydrogenase	BUA36_RS15000	BUA36_RS13005
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	BUA36_RS04095	BUA36_RS27625
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BUA36_RS22500	BUA36_RS26910
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BUA36_RS22495	BUA36_RS26915
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BUA36_RS26915	BUA36_RS22490
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BUA36_RS26920	BUA36_RS22485
D-LDH	D-lactate dehydrogenase	BUA36_RS09525	BUA36_RS27965
dddA	3-hydroxypropionate dehydrogenase	BUA36_RS07265
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	BUA36_RS08655
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BUA36_RS13895	BUA36_RS27965
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BUA36_RS13890
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BUA36_RS13885
gloA	glyoxylase I	BUA36_RS14815
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BUA36_RS28065	BUA36_RS10090
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	BUA36_RS19960	BUA36_RS12660
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BUA36_RS12915	BUA36_RS12670
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BUA36_RS04305	BUA36_RS15370
L-LDH	L-lactate dehydrogenase	BUA36_RS24315
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BUA36_RS21035
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BUA36_RS27965
lctO	L-lactate oxidase or 2-monooxygenase	BUA36_RS24315
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	BUA36_RS08685	BUA36_RS23520
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BUA36_RS08685
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BUA36_RS08685	BUA36_RS23520
pccA	propionyl-CoA carboxylase, alpha subunit	BUA36_RS07760	BUA36_RS28720
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BUA36_RS28720	BUA36_RS07760
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BUA36_RS07795
pco	propanyl-CoA oxidase	BUA36_RS15230
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BUA36_RS09240	BUA36_RS28635
prpC	2-methylcitrate synthase	BUA36_RS28630	BUA36_RS01855
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	BUA36_RS28620
pta	phosphate acetyltransferase	BUA36_RS04820	BUA36_RS15335
serP1	L-threonine uptake transporter SerP1	BUA36_RS06065	BUA36_RS24700
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	BUA36_RS18985	BUA36_RS25770
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BUA36_RS04310	BUA36_RS07230
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BUA36_RS30010	BUA36_RS26930

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.