L-threonine catabolism in Mycolicibacterium vanbaalenii PYR-1

Best path

braC, braD, braE, braF, braG, ltaE, adh, ackA, pta, 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)
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	MVAN_RS14285	MVAN_RS13035
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	MVAN_RS14290
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	MVAN_RS14295	MVAN_RS13025
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	MVAN_RS14300	MVAN_RS13020
ltaE	L-threonine aldolase	MVAN_RS05945	MVAN_RS23385
adh	acetaldehyde dehydrogenase (not acylating)	MVAN_RS07400	MVAN_RS01230
ackA	acetate kinase	MVAN_RS03540	MVAN_RS23500
pta	phosphate acetyltransferase	MVAN_RS03535
gcvP	glycine cleavage system, P component (glycine decarboxylase)	MVAN_RS15715
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	MVAN_RS17945	MVAN_RS06060
gcvH	glycine cleavage system, H component (lipoyl protein)	MVAN_RS15740
lpd	dihydrolipoyl dehydrogenase	MVAN_RS04005	MVAN_RS12275
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	MVAN_RS13785
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	MVAN_RS13785
acs	acetyl-CoA synthetase, AMP-forming	MVAN_RS27275	MVAN_RS07110
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	MVAN_RS02255	MVAN_RS22065
aldA	lactaldehyde dehydrogenase	MVAN_RS06715	MVAN_RS07400
D-LDH	D-lactate dehydrogenase	MVAN_RS22430	MVAN_RS22475
dddA	3-hydroxypropionate dehydrogenase	MVAN_RS14770	MVAN_RS29655
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	MVAN_RS13610
epi	methylmalonyl-CoA epimerase	MVAN_RS21600
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	MVAN_RS22430
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	MVAN_RS29170
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	MVAN_RS13005	MVAN_RS16760
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	MVAN_RS23515	MVAN_RS23045
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	MVAN_RS06885	MVAN_RS09180
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	MVAN_RS14010
L-LDH	L-lactate dehydrogenase	MVAN_RS02235	MVAN_RS06560
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	MVAN_RS10525
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	MVAN_RS10530
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	MVAN_RS22430
lctO	L-lactate oxidase or 2-monooxygenase	MVAN_RS11060	MVAN_RS06560
lldE	L-lactate dehydrogenase, LldE subunit	MVAN_RS13605
lldF	L-lactate dehydrogenase, LldF subunit	MVAN_RS13610
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	MVAN_RS13605
lutB	L-lactate dehydrogenase, LutB subunit	MVAN_RS13610
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	MVAN_RS13875	MVAN_RS21370
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	MVAN_RS21365	MVAN_RS13875
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	MVAN_RS13875	MVAN_RS21370
pccA	propionyl-CoA carboxylase, alpha subunit	MVAN_RS08390	MVAN_RS20500
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	MVAN_RS20500	MVAN_RS08390
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	MVAN_RS20500
pccB	propionyl-CoA carboxylase, beta subunit	MVAN_RS08455	MVAN_RS28370
pco	propanyl-CoA oxidase	MVAN_RS19075	MVAN_RS23465
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	MVAN_RS14955	MVAN_RS04040
prpC	2-methylcitrate synthase	MVAN_RS25255	MVAN_RS25240
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
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	MVAN_RS13975	MVAN_RS15175
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	MVAN_RS27530	MVAN_RS27545
tynA	aminoacetone oxidase	MVAN_RS11120	MVAN_RS17105
yvgN	methylglyoxal reductase (NADPH-dependent)	MVAN_RS08905	MVAN_RS10840

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.