L-threonine catabolism in Marinobacter algicola DG893

Best path

braC, braD, braE, braF, braG, tdcB, tdcE, prpC, acnD, prpF, acn, prpB

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 (52 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)	MDG893_RS07210
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	MDG893_RS07215	MDG893_RS18900
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	MDG893_RS07220	MDG893_RS16830
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	MDG893_RS08225	MDG893_RS07225
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	MDG893_RS07230	MDG893_RS16820
tdcB	L-threonine dehydratase	MDG893_RS12510
tdcE	2-ketobutyrate formate-lyase
prpC	2-methylcitrate synthase	MDG893_RS04325	MDG893_RS03515
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	MDG893_RS04330	MDG893_RS17680
prpF	methylaconitate isomerase	MDG893_RS04335	MDG893_RS09680
acn	(2R,3S)-2-methylcitrate dehydratase	MDG893_RS04330	MDG893_RS12040
prpB	2-methylisocitrate lyase	MDG893_RS04320
Alternative steps:
ackA	acetate kinase	MDG893_RS15690
acs	acetyl-CoA synthetase, AMP-forming	MDG893_RS01990	MDG893_RS04045
adh	acetaldehyde dehydrogenase (not acylating)	MDG893_RS07565	MDG893_RS18610
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	MDG893_RS03885
aldA	lactaldehyde dehydrogenase	MDG893_RS14400	MDG893_RS07565
D-LDH	D-lactate dehydrogenase	MDG893_RS13945	MDG893_RS08825
dddA	3-hydroxypropionate dehydrogenase	MDG893_RS13420
DVU3032	L-lactate dehydrogenase, LutC-like component	MDG893_RS19595
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	MDG893_RS19590
epi	methylmalonyl-CoA epimerase
gcvH	glycine cleavage system, H component (lipoyl protein)	MDG893_RS14855
gcvP	glycine cleavage system, P component (glycine decarboxylase)
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	MDG893_RS01525
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	MDG893_RS08825
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	MDG893_RS08820
glcF	D-lactate dehydrogenase, FeS subunit GlcF	MDG893_RS08815
gloA	glyoxylase I	MDG893_RS19605	MDG893_RS00835
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	MDG893_RS15490	MDG893_RS09330
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	MDG893_RS16740	MDG893_RS16745
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	MDG893_RS05705	MDG893_RS06945
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	MDG893_RS15805
L-LDH	L-lactate dehydrogenase	MDG893_RS09925
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	MDG893_RS02405
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component
lctO	L-lactate oxidase or 2-monooxygenase	MDG893_RS09925
lldE	L-lactate dehydrogenase, LldE subunit	MDG893_RS19585
lldF	L-lactate dehydrogenase, LldF subunit	MDG893_RS19590
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	MDG893_RS03480	MDG893_RS16040
ltaE	L-threonine aldolase	MDG893_RS05100	MDG893_RS19485
lutA	L-lactate dehydrogenase, LutA subunit	MDG893_RS19585
lutB	L-lactate dehydrogenase, LutB subunit	MDG893_RS19590
lutC	L-lactate dehydrogenase, LutC subunit	MDG893_RS19595
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	MDG893_RS00040
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	MDG893_RS00055
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	MDG893_RS00040
pccA	propionyl-CoA carboxylase, alpha subunit	MDG893_RS20190	MDG893_RS14185
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	MDG893_RS18380	MDG893_RS12555
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	MDG893_RS18375
pccB	propionyl-CoA carboxylase, beta subunit	MDG893_RS14175	MDG893_RS20235
pco	propanyl-CoA oxidase	MDG893_RS18850	MDG893_RS11060
phtA	L-threonine uptake permease PhtA
prpD	2-methylcitrate dehydratase	MDG893_RS04350
pta	phosphate acetyltransferase
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT	MDG893_RS05550
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	MDG893_RS07530	MDG893_RS13520
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	MDG893_RS01890

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.