L-threonine catabolism in Derxia gummosa DSM 723

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 (50 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)	H566_RS0117030
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	H566_RS0102680	H566_RS0104990
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	H566_RS22525	H566_RS0104985
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	H566_RS0102690	H566_RS0111715
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	H566_RS0102695	H566_RS0113085
ltaE	L-threonine aldolase	H566_RS0104140	H566_RS0104925
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	H566_RS0111655
gcvP	glycine cleavage system, P component (glycine decarboxylase)	H566_RS0101780
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	H566_RS0101790	H566_RS0107295
gcvH	glycine cleavage system, H component (lipoyl protein)	H566_RS0101785
lpd	dihydrolipoyl dehydrogenase	H566_RS0117905	H566_RS0121210
Alternative steps:
ackA	acetate kinase	H566_RS0120655	H566_RS0121200
acn	(2R,3S)-2-methylcitrate dehydratase	H566_RS0121280	H566_RS0121290
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	H566_RS0121280	H566_RS0121365
acs	acetyl-CoA synthetase, AMP-forming	H566_RS0119605	H566_RS0120475
adh	acetaldehyde dehydrogenase (not acylating)	H566_RS0101815	H566_RS0108130
aldA	lactaldehyde dehydrogenase	H566_RS0120955	H566_RS0101815
D-LDH	D-lactate dehydrogenase	H566_RS0109250	H566_RS0118935
dddA	3-hydroxypropionate dehydrogenase	H566_RS0105035
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	H566_RS0109255
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	H566_RS0108475	H566_RS0118935
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	H566_RS0108480
glcF	D-lactate dehydrogenase, FeS subunit GlcF	H566_RS0108485
gloA	glyoxylase I	H566_RS0121905	H566_RS0111935
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	H566_RS0107875	H566_RS0102275
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	H566_RS0118410	H566_RS0111180
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	H566_RS0112430	H566_RS0120495
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	H566_RS0115730	H566_RS21955
L-LDH	L-lactate dehydrogenase	H566_RS0112175	H566_RS25910
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	H566_RS0103900
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	H566_RS0103905	H566_RS0106280
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	H566_RS0118935
lctO	L-lactate oxidase or 2-monooxygenase	H566_RS0112175	H566_RS25910
lldE	L-lactate dehydrogenase, LldE subunit	H566_RS0109265
lldF	L-lactate dehydrogenase, LldF subunit	H566_RS0109255
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	H566_RS0109265
lutB	L-lactate dehydrogenase, LutB subunit	H566_RS0109255
lutC	L-lactate dehydrogenase, LutC subunit	H566_RS0109260
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	H566_RS24885
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	H566_RS24885
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	H566_RS24885
pccA	propionyl-CoA carboxylase, alpha subunit	H566_RS0105270	H566_RS0110680
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	H566_RS0105270	H566_RS0110680
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit
pco	propanyl-CoA oxidase	H566_RS25545
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	H566_RS0108095	H566_RS0121270
prpC	2-methylcitrate synthase	H566_RS0121275	H566_RS0121225
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	H566_RS0121285	H566_RS0116655
pta	phosphate acetyltransferase	H566_RS26885	H566_RS0106505
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	H566_RS0105405
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	H566_RS0101475	H566_RS0116360
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.