L-threonine catabolism in Microvirga lotononidis WSM3557

Best path

braC, braD, braE, braF, braG, tdcB, tdcE, pccA, pccB, epi, mcmA

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
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	MICLODRAFT_RS30935	MICLODRAFT_RS25195
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	MICLODRAFT_RS30910	MICLODRAFT_RS11965
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	MICLODRAFT_RS30915	MICLODRAFT_RS27010
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	MICLODRAFT_RS27005	MICLODRAFT_RS30920
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	MICLODRAFT_RS30925	MICLODRAFT_RS11955
tdcB	L-threonine dehydratase	MICLODRAFT_RS33510	MICLODRAFT_RS10110
tdcE	2-ketobutyrate formate-lyase	MICLODRAFT_RS17155
pccA	propionyl-CoA carboxylase, alpha subunit	MICLODRAFT_RS25320	MICLODRAFT_RS26375
pccB	propionyl-CoA carboxylase, beta subunit	MICLODRAFT_RS23515	MICLODRAFT_RS25395
epi	methylmalonyl-CoA epimerase	MICLODRAFT_RS10315
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	MICLODRAFT_RS30350
Alternative steps:
ackA	acetate kinase	MICLODRAFT_RS09085	MICLODRAFT_RS12250
acn	(2R,3S)-2-methylcitrate dehydratase	MICLODRAFT_RS07815	MICLODRAFT_RS09000
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	MICLODRAFT_RS07815	MICLODRAFT_RS09000
acs	acetyl-CoA synthetase, AMP-forming	MICLODRAFT_RS29080	MICLODRAFT_RS22300
adh	acetaldehyde dehydrogenase (not acylating)	MICLODRAFT_RS21540	MICLODRAFT_RS17515
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	MICLODRAFT_RS22470	MICLODRAFT_RS31070
D-LDH	D-lactate dehydrogenase	MICLODRAFT_RS22070	MICLODRAFT_RS17165
dddA	3-hydroxypropionate dehydrogenase	MICLODRAFT_RS20145	MICLODRAFT_RS24005
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	MICLODRAFT_RS20980
gcvH	glycine cleavage system, H component (lipoyl protein)	MICLODRAFT_RS32795
gcvP	glycine cleavage system, P component (glycine decarboxylase)	MICLODRAFT_RS32810	MICLODRAFT_RS32805
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	MICLODRAFT_RS32790
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	MICLODRAFT_RS20995	MICLODRAFT_RS22070
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	MICLODRAFT_RS21000
glcF	D-lactate dehydrogenase, FeS subunit GlcF	MICLODRAFT_RS21010
gloA	glyoxylase I	MICLODRAFT_RS29935	MICLODRAFT_RS08640
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	MICLODRAFT_RS16920	MICLODRAFT_RS27950
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	MICLODRAFT_RS07440	MICLODRAFT_RS29860
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	MICLODRAFT_RS17490	MICLODRAFT_RS27600
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	MICLODRAFT_RS31450	MICLODRAFT_RS03110
L-LDH	L-lactate dehydrogenase	MICLODRAFT_RS28670	MICLODRAFT_RS29700
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	MICLODRAFT_RS00035
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	MICLODRAFT_RS00030	MICLODRAFT_RS18335
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	MICLODRAFT_RS22070	MICLODRAFT_RS20995
lctO	L-lactate oxidase or 2-monooxygenase	MICLODRAFT_RS20840	MICLODRAFT_RS29700
lldE	L-lactate dehydrogenase, LldE subunit	MICLODRAFT_RS20985
lldF	L-lactate dehydrogenase, LldF subunit	MICLODRAFT_RS20980
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	MICLODRAFT_RS26735	MICLODRAFT_RS10555
ltaE	L-threonine aldolase	MICLODRAFT_RS18715	MICLODRAFT_RS10145
lutA	L-lactate dehydrogenase, LutA subunit	MICLODRAFT_RS20985
lutB	L-lactate dehydrogenase, LutB subunit	MICLODRAFT_RS20980
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	MICLODRAFT_RS30350
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	MICLODRAFT_RS30350
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	MICLODRAFT_RS25320	MICLODRAFT_RS09320
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	MICLODRAFT_RS17745	MICLODRAFT_RS25365
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	MICLODRAFT_RS28970	MICLODRAFT_RS23955
prpC	2-methylcitrate synthase	MICLODRAFT_RS10420	MICLODRAFT_RS33180
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	MICLODRAFT_RS29625
pta	phosphate acetyltransferase	MICLODRAFT_RS09080	MICLODRAFT_RS19205
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	MICLODRAFT_RS24770
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	MICLODRAFT_RS28040	MICLODRAFT_RS11280
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	MICLODRAFT_RS21090	MICLODRAFT_RS04815

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.