L-threonine catabolism in Brucella inopinata BO1

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 (48 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)	BIBO1_RS12225	BIBO1_RS06815
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BIBO1_RS12250	BIBO1_RS14975
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BIBO1_RS12245
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BIBO1_RS19765	BIBO1_RS12240
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BIBO1_RS12235	BIBO1_RS14990
ltaE	L-threonine aldolase	BIBO1_RS14860	BIBO1_RS07260
adh	acetaldehyde dehydrogenase (not acylating)	BIBO1_RS10835	BIBO1_RS11605
acs	acetyl-CoA synthetase, AMP-forming	BIBO1_RS12340	BIBO1_RS12015
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BIBO1_RS16930
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BIBO1_RS16920	BIBO1_RS12740
gcvH	glycine cleavage system, H component (lipoyl protein)	BIBO1_RS16925
lpd	dihydrolipoyl dehydrogenase	BIBO1_RS17510	BIBO1_RS08610
Alternative steps:
ackA	acetate kinase	BIBO1_RS16460
acn	(2R,3S)-2-methylcitrate dehydratase	BIBO1_RS10365
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BIBO1_RS10365
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	BIBO1_RS19460	BIBO1_RS14100
D-LDH	D-lactate dehydrogenase	BIBO1_RS10100	BIBO1_RS13480
dddA	3-hydroxypropionate dehydrogenase	BIBO1_RS19010	BIBO1_RS15375
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	BIBO1_RS07490
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BIBO1_RS15670	BIBO1_RS10100
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BIBO1_RS15675
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BIBO1_RS15680
gloA	glyoxylase I	BIBO1_RS19195	BIBO1_RS09435
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BIBO1_RS05750	BIBO1_RS11085
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	BIBO1_RS06755	BIBO1_RS15870
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BIBO1_RS12430	BIBO1_RS10860
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BIBO1_RS13145	BIBO1_RS17370
L-LDH	L-lactate dehydrogenase	BIBO1_RS18825	BIBO1_RS05715
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BIBO1_RS05850
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BIBO1_RS15670	BIBO1_RS13480
lctO	L-lactate oxidase or 2-monooxygenase	BIBO1_RS18825
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit
lutB	L-lactate dehydrogenase, LutB subunit
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	BIBO1_RS09070
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BIBO1_RS09070
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BIBO1_RS09070
pccA	propionyl-CoA carboxylase, alpha subunit	BIBO1_RS09065	BIBO1_RS06830
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BIBO1_RS09065	BIBO1_RS07715
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	BIBO1_RS12215
pccB	propionyl-CoA carboxylase, beta subunit	BIBO1_RS09060	BIBO1_RS06835
pco	propanyl-CoA oxidase	BIBO1_RS08430	BIBO1_RS17185
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BIBO1_RS11515
prpC	2-methylcitrate synthase	BIBO1_RS08705
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	BIBO1_RS10585	BIBO1_RS08120
RR42_RS28305	L-threonine:H+ symporter	BIBO1_RS14845
serP1	L-threonine uptake transporter SerP1	BIBO1_RS14845
snatA	L-threonine transporter snatA	BIBO1_RS08495
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	BIBO1_RS08275
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BIBO1_RS10840	BIBO1_RS16475
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BIBO1_RS15685

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.