L-threonine catabolism in Rhodomicrobium vannielii ATCC 17100

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 (53 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
snatA	L-threonine transporter snatA	RVAN_RS10695
ltaE	L-threonine aldolase	RVAN_RS03675
adh	acetaldehyde dehydrogenase (not acylating)	RVAN_RS09190	RVAN_RS11750
acs	acetyl-CoA synthetase, AMP-forming	RVAN_RS08390	RVAN_RS18025
gcvP	glycine cleavage system, P component (glycine decarboxylase)	RVAN_RS00150	RVAN_RS00155
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	RVAN_RS00165
gcvH	glycine cleavage system, H component (lipoyl protein)	RVAN_RS00160
lpd	dihydrolipoyl dehydrogenase	RVAN_RS06680	RVAN_RS03245
Alternative steps:
ackA	acetate kinase	RVAN_RS14645
acn	(2R,3S)-2-methylcitrate dehydratase	RVAN_RS09985	RVAN_RS05815
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	RVAN_RS05815
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	RVAN_RS17190
aldA	lactaldehyde dehydrogenase	RVAN_RS09190	RVAN_RS11750
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	RVAN_RS04095
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	RVAN_RS04120	RVAN_RS09275
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	RVAN_RS19490	RVAN_RS14870
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	RVAN_RS04490	RVAN_RS04110
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	RVAN_RS04105	RVAN_RS14875
D-LDH	D-lactate dehydrogenase	RVAN_RS09860	RVAN_RS03890
dddA	3-hydroxypropionate dehydrogenase	RVAN_RS08470
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	RVAN_RS03720
epi	methylmalonyl-CoA epimerase	RVAN_RS18295
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	RVAN_RS16250	RVAN_RS03890
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	RVAN_RS16245
glcF	D-lactate dehydrogenase, FeS subunit GlcF	RVAN_RS16240
gloA	glyoxylase I	RVAN_RS02530	RVAN_RS03850
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	RVAN_RS11785
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	RVAN_RS11250	RVAN_RS17115
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	RVAN_RS17095	RVAN_RS11750
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	RVAN_RS17540	RVAN_RS17350
L-LDH	L-lactate dehydrogenase	RVAN_RS04465	RVAN_RS03215
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	RVAN_RS05665
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	RVAN_RS05660	RVAN_RS17555
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	RVAN_RS16250	RVAN_RS03890
lctO	L-lactate oxidase or 2-monooxygenase	RVAN_RS04465
lldE	L-lactate dehydrogenase, LldE subunit	RVAN_RS18380
lldF	L-lactate dehydrogenase, LldF subunit	RVAN_RS03720
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	RVAN_RS18380
lutB	L-lactate dehydrogenase, LutB subunit	RVAN_RS03720
lutC	L-lactate dehydrogenase, LutC subunit	RVAN_RS03715
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	RVAN_RS10880	RVAN_RS05750
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	RVAN_RS10880	RVAN_RS05750
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	RVAN_RS10880	RVAN_RS05750
pccA	propionyl-CoA carboxylase, alpha subunit	RVAN_RS13015	RVAN_RS03495
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	RVAN_RS13015	RVAN_RS17145
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	RVAN_RS05785	RVAN_RS03490
pco	propanyl-CoA oxidase	RVAN_RS09295	RVAN_RS03505
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	RVAN_RS09205
prpC	2-methylcitrate synthase	RVAN_RS09210	RVAN_RS16075
prpD	2-methylcitrate dehydratase	RVAN_RS09215
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	RVAN_RS07875	RVAN_RS01300
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	RVAN_RS04340	RVAN_RS10775
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	RVAN_RS05170
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.