L-threonine catabolism in Halobacillus alkaliphilus FP5

Best path

tdcC, 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 (44 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
tdcC	L-threonine:H+ symporter TdcC
ltaE	L-threonine aldolase	BMZ06_RS04115	BMZ06_RS06845
adh	acetaldehyde dehydrogenase (not acylating)	BMZ06_RS08010	BMZ06_RS19550
ackA	acetate kinase	BMZ06_RS18185	BMZ06_RS13245
pta	phosphate acetyltransferase	BMZ06_RS06610	BMZ06_RS01085
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BMZ06_RS00885	BMZ06_RS00880
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BMZ06_RS00875
gcvH	glycine cleavage system, H component (lipoyl protein)	BMZ06_RS09255
lpd	dihydrolipoyl dehydrogenase	BMZ06_RS10225	BMZ06_RS01100
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	BMZ06_RS19330
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BMZ06_RS19330
acs	acetyl-CoA synthetase, AMP-forming	BMZ06_RS17975	BMZ06_RS02730
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	BMZ06_RS17960	BMZ06_RS17530
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)	BMZ06_RS07280
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BMZ06_RS07270	BMZ06_RS07265
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BMZ06_RS07265	BMZ06_RS07270
D-LDH	D-lactate dehydrogenase	BMZ06_RS16810	BMZ06_RS16855
dddA	3-hydroxypropionate dehydrogenase	BMZ06_RS07640	BMZ06_RS18265
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	BMZ06_RS01155	BMZ06_RS13600
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BMZ06_RS16855	BMZ06_RS16810
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BMZ06_RS16855
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BMZ06_RS16850
gloA	glyoxylase I	BMZ06_RS18475	BMZ06_RS07895
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BMZ06_RS01855	BMZ06_RS00805
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	BMZ06_RS18940	BMZ06_RS02720
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BMZ06_RS10420	BMZ06_RS09860
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BMZ06_RS05825
L-LDH	L-lactate dehydrogenase	BMZ06_RS01565	BMZ06_RS00755
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BMZ06_RS18950
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BMZ06_RS16855	BMZ06_RS16810
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	BMZ06_RS16850
lutB	L-lactate dehydrogenase, LutB subunit
lutC	L-lactate dehydrogenase, LutC subunit
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	BMZ06_RS01150	BMZ06_RS06725
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BMZ06_RS01155	BMZ06_RS06725
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BMZ06_RS06725	BMZ06_RS01150
pccA	propionyl-CoA carboxylase, alpha subunit	BMZ06_RS00985	BMZ06_RS02705
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BMZ06_RS00985	BMZ06_RS02705
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BMZ06_RS01160	BMZ06_RS02725
pco	propanyl-CoA oxidase	BMZ06_RS06705	BMZ06_RS02695
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BMZ06_RS09405	BMZ06_RS18870
prpC	2-methylcitrate synthase	BMZ06_RS12400
prpD	2-methylcitrate dehydratase	BMZ06_RS18865
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	BMZ06_RS17650	BMZ06_RS17165
tdcE	2-ketobutyrate formate-lyase	BMZ06_RS17415
tdh	L-threonine 3-dehydrogenase	BMZ06_RS05820	BMZ06_RS02210
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BMZ06_RS17495	BMZ06_RS13655

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.