L-threonine catabolism in Belnapia rosea CPCC 100156

Best path

braC, braD, braE, braF, braG, ltaE, adh, acs, 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)	BLR02_RS12505
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BLR02_RS12525	BLR02_RS19370
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BLR02_RS12520	BLR02_RS25430
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BLR02_RS12515	BLR02_RS03485
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BLR02_RS12510	BLR02_RS10300
ltaE	L-threonine aldolase	BLR02_RS01970	BLR02_RS04215
adh	acetaldehyde dehydrogenase (not acylating)	BLR02_RS07320	BLR02_RS18460
acs	acetyl-CoA synthetase, AMP-forming	BLR02_RS09295	BLR02_RS17730
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BLR02_RS15325
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BLR02_RS15335
gcvH	glycine cleavage system, H component (lipoyl protein)	BLR02_RS15330
lpd	dihydrolipoyl dehydrogenase	BLR02_RS01950	BLR02_RS16900
Alternative steps:
ackA	acetate kinase	BLR02_RS16785
acn	(2R,3S)-2-methylcitrate dehydratase	BLR02_RS06435
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BLR02_RS06435
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	BLR02_RS04250	BLR02_RS07320
D-LDH	D-lactate dehydrogenase	BLR02_RS13975	BLR02_RS19165
dddA	3-hydroxypropionate dehydrogenase	BLR02_RS18510	BLR02_RS02205
DVU3032	L-lactate dehydrogenase, LutC-like component	BLR02_RS08915
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	BLR02_RS08910
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BLR02_RS08760	BLR02_RS13975
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BLR02_RS08765	BLR02_RS18505
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BLR02_RS08785	BLR02_RS18265
gloA	glyoxylase I	BLR02_RS05210	BLR02_RS16530
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BLR02_RS00015	BLR02_RS17670
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	BLR02_RS23955	BLR02_RS08090
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BLR02_RS18460	BLR02_RS07320
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BLR02_RS13350	BLR02_RS19580
L-LDH	L-lactate dehydrogenase	BLR02_RS22460	BLR02_RS22355
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BLR02_RS25820
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BLR02_RS13975	BLR02_RS08760
lctO	L-lactate oxidase or 2-monooxygenase	BLR02_RS05520
lldE	L-lactate dehydrogenase, LldE subunit	BLR02_RS18265
lldF	L-lactate dehydrogenase, LldF subunit	BLR02_RS08910
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	BLR02_RS18265
lutB	L-lactate dehydrogenase, LutB subunit	BLR02_RS08910
lutC	L-lactate dehydrogenase, LutC subunit	BLR02_RS08915
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
pccA	propionyl-CoA carboxylase, alpha subunit	BLR02_RS03535	BLR02_RS01010
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BLR02_RS01010	BLR02_RS23135
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	BLR02_RS03535
pccB	propionyl-CoA carboxylase, beta subunit	BLR02_RS03530	BLR02_RS23125
pco	propanyl-CoA oxidase	BLR02_RS06730
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BLR02_RS15615	BLR02_RS04390
prpC	2-methylcitrate synthase	BLR02_RS19010	BLR02_RS05735
prpD	2-methylcitrate dehydratase	BLR02_RS19020
prpF	methylaconitate isomerase	BLR02_RS04850	BLR02_RS20970
pta	phosphate acetyltransferase	BLR02_RS16780	BLR02_RS20655
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	BLR02_RS18970	BLR02_RS15635
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BLR02_RS07915	BLR02_RS05380
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BLR02_RS23585	BLR02_RS01590

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.