L-threonine catabolism in Cereibacter sphaeroides ATCC 17029

Best path

snatA, 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 (46 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
snatA	L-threonine transporter snatA	RSPH17029_RS07790
ltaE	L-threonine aldolase	RSPH17029_RS00510	RSPH17029_RS04985
adh	acetaldehyde dehydrogenase (not acylating)	RSPH17029_RS17490	RSPH17029_RS13480
acs	acetyl-CoA synthetase, AMP-forming	RSPH17029_RS11250	RSPH17029_RS01250
gcvP	glycine cleavage system, P component (glycine decarboxylase)	RSPH17029_RS04430
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	RSPH17029_RS04420	RSPH17029_RS06825
gcvH	glycine cleavage system, H component (lipoyl protein)	RSPH17029_RS04425
lpd	dihydrolipoyl dehydrogenase	RSPH17029_RS08165	RSPH17029_RS13225
Alternative steps:
ackA	acetate kinase	RSPH17029_RS14695
acn	(2R,3S)-2-methylcitrate dehydratase	RSPH17029_RS02300
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	RSPH17029_RS02300
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	RSPH17029_RS16005	RSPH17029_RS04350
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	RSPH17029_RS07930
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	RSPH17029_RS07945	RSPH17029_RS17970
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	RSPH17029_RS17975	RSPH17029_RS04845
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	RSPH17029_RS07935	RSPH17029_RS14865
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	RSPH17029_RS07940	RSPH17029_RS04835
D-LDH	D-lactate dehydrogenase	RSPH17029_RS04045	RSPH17029_RS09160
dddA	3-hydroxypropionate dehydrogenase	RSPH17029_RS20315	RSPH17029_RS04355
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	RSPH17029_RS12460
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	RSPH17029_RS13520	RSPH17029_RS04045
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	RSPH17029_RS13515
glcF	D-lactate dehydrogenase, FeS subunit GlcF	RSPH17029_RS13510
gloA	glyoxylase I	RSPH17029_RS20070	RSPH17029_RS19105
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	RSPH17029_RS04945	RSPH17029_RS12665
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	RSPH17029_RS00050	RSPH17029_RS06550
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	RSPH17029_RS08140	RSPH17029_RS04350
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	RSPH17029_RS05290	RSPH17029_RS08245
L-LDH	L-lactate dehydrogenase	RSPH17029_RS12550	RSPH17029_RS13255
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	RSPH17029_RS01640
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	RSPH17029_RS04045	RSPH17029_RS13520
lctO	L-lactate oxidase or 2-monooxygenase	RSPH17029_RS12550
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	RSPH17029_RS04415	RSPH17029_RS18485
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	RSPH17029_RS04415	RSPH17029_RS18470
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	RSPH17029_RS04415	RSPH17029_RS18485
pccA	propionyl-CoA carboxylase, alpha subunit	RSPH17029_RS04405	RSPH17029_RS05950
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	RSPH17029_RS04405	RSPH17029_RS09225
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	RSPH17029_RS09220
pccB	propionyl-CoA carboxylase, beta subunit	RSPH17029_RS04380	RSPH17029_RS05945
pco	propanyl-CoA oxidase	RSPH17029_RS14905
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	RSPH17029_RS03595
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	RSPH17029_RS18095	RSPH17029_RS18235
pta	phosphate acetyltransferase	RSPH17029_RS14700	RSPH17029_RS14510
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	RSPH17029_RS14480	RSPH17029_RS04715
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	RSPH17029_RS05295	RSPH17029_RS05055
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	RSPH17029_RS05040

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 10 2024. The underlying query database was built on Sep 17 2021.