L-threonine catabolism in Streptacidiphilus oryzae TH49

Best path

braC, braD, braE, braF, braG, tdcB, tdcE, pccA, pccB, epi, mcm-large, mcm-small

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 (49 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)
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BS73_RS29125	BS73_RS13625
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BS73_RS29120	BS73_RS13630
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BS73_RS00335	BS73_RS29115
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BS73_RS00340	BS73_RS29110
tdcB	L-threonine dehydratase	BS73_RS16930	BS73_RS17825
tdcE	2-ketobutyrate formate-lyase	BS73_RS30625
pccA	propionyl-CoA carboxylase, alpha subunit	BS73_RS23635	BS73_RS25280
pccB	propionyl-CoA carboxylase, beta subunit	BS73_RS07330	BS73_RS24900
epi	methylmalonyl-CoA epimerase	BS73_RS15090
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	BS73_RS07325	BS73_RS15040
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BS73_RS23175	BS73_RS11855
Alternative steps:
ackA	acetate kinase	BS73_RS15005
acn	(2R,3S)-2-methylcitrate dehydratase	BS73_RS12710
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BS73_RS12710
acs	acetyl-CoA synthetase, AMP-forming	BS73_RS20690	BS73_RS01530
adh	acetaldehyde dehydrogenase (not acylating)	BS73_RS04090	BS73_RS01745
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	BS73_RS10620	BS73_RS23595
D-LDH	D-lactate dehydrogenase	BS73_RS04910	BS73_RS24465
dddA	3-hydroxypropionate dehydrogenase	BS73_RS13540	BS73_RS01415
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	BS73_RS03925	BS73_RS10140
gcvH	glycine cleavage system, H component (lipoyl protein)	BS73_RS14875
gcvP	glycine cleavage system, P component (glycine decarboxylase)
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BS73_RS14870
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BS73_RS24465	BS73_RS04750
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BS73_RS04750
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BS73_RS10415	BS73_RS08575
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	BS73_RS20300	BS73_RS14910
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BS73_RS14210	BS73_RS14255
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BS73_RS00515	BS73_RS34050
L-LDH	L-lactate dehydrogenase	BS73_RS07640	BS73_RS01430
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BS73_RS09575
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BS73_RS24465	BS73_RS04750
lctO	L-lactate oxidase or 2-monooxygenase	BS73_RS10185	BS73_RS07640
lldE	L-lactate dehydrogenase, LldE subunit	BS73_RS10145	BS73_RS03920
lldF	L-lactate dehydrogenase, LldF subunit	BS73_RS10140	BS73_RS03925
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	BS73_RS01320	BS73_RS28205
ltaE	L-threonine aldolase	BS73_RS09615	BS73_RS14880
lutA	L-lactate dehydrogenase, LutA subunit	BS73_RS10145	BS73_RS03920
lutB	L-lactate dehydrogenase, LutB subunit	BS73_RS10140	BS73_RS03925
lutC	L-lactate dehydrogenase, LutC subunit
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BS73_RS07325	BS73_RS15040
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BS73_RS23635	BS73_RS06500
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	BS73_RS32915
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BS73_RS29705	BS73_RS10660
prpC	2-methylcitrate synthase	BS73_RS25400	BS73_RS17760
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	BS73_RS10825	BS73_RS31830
pta	phosphate acetyltransferase
RR42_RS28305	L-threonine:H+ symporter	BS73_RS16535	BS73_RS10785
serP1	L-threonine uptake transporter SerP1	BS73_RS10785	BS73_RS16535
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	BS73_RS16880	BS73_RS10410
tynA	aminoacetone oxidase	BS73_RS10580
yvgN	methylglyoxal reductase (NADPH-dependent)	BS73_RS07605	BS73_RS38120

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.