L-threonine catabolism in Azospirillum humicireducens SgZ-5

Best path

braC, braD, braE, braF, braG, tdcB, tdcE, pccA, pccB, epi, mcm-large, mcm-small

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 (57 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)	A6A40_RS30135	A6A40_RS13365
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	A6A40_RS13390	A6A40_RS09880
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	A6A40_RS13385	A6A40_RS22595
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	A6A40_RS13380	A6A40_RS10200
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	A6A40_RS13375	A6A40_RS20105
tdcB	L-threonine dehydratase	A6A40_RS19110	A6A40_RS29175
tdcE	2-ketobutyrate formate-lyase	A6A40_RS30195
pccA	propionyl-CoA carboxylase, alpha subunit	A6A40_RS28245	A6A40_RS19645
pccB	propionyl-CoA carboxylase, beta subunit	A6A40_RS28240	A6A40_RS19635
epi	methylmalonyl-CoA epimerase	A6A40_RS08555
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	A6A40_RS28250
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	A6A40_RS28250
Alternative steps:
ackA	acetate kinase	A6A40_RS02540	A6A40_RS29385
acn	(2R,3S)-2-methylcitrate dehydratase	A6A40_RS30175	A6A40_RS10110
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	A6A40_RS10110
acs	acetyl-CoA synthetase, AMP-forming	A6A40_RS10075	A6A40_RS08675
adh	acetaldehyde dehydrogenase (not acylating)	A6A40_RS26775	A6A40_RS21130
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	A6A40_RS21750
aldA	lactaldehyde dehydrogenase	A6A40_RS29725	A6A40_RS26775
D-LDH	D-lactate dehydrogenase	A6A40_RS13765	A6A40_RS03075
dddA	3-hydroxypropionate dehydrogenase	A6A40_RS28085	A6A40_RS13555
DVU3032	L-lactate dehydrogenase, LutC-like component	A6A40_RS13780
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	A6A40_RS13775
gcvH	glycine cleavage system, H component (lipoyl protein)	A6A40_RS05625
gcvP	glycine cleavage system, P component (glycine decarboxylase)	A6A40_RS05615	A6A40_RS05620
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	A6A40_RS05630	A6A40_RS18210
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	A6A40_RS01420	A6A40_RS03075
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	A6A40_RS01425
glcF	D-lactate dehydrogenase, FeS subunit GlcF	A6A40_RS01430	A6A40_RS13770
gloA	glyoxylase I	A6A40_RS04615	A6A40_RS19405
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	A6A40_RS29280	A6A40_RS13630
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	A6A40_RS14715	A6A40_RS26605
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	A6A40_RS18190	A6A40_RS25750
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	A6A40_RS10865
L-LDH	L-lactate dehydrogenase	A6A40_RS14785	A6A40_RS11670
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	A6A40_RS02195
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	A6A40_RS02200	A6A40_RS00355
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	A6A40_RS03075	A6A40_RS01420
lctO	L-lactate oxidase or 2-monooxygenase	A6A40_RS14785	A6A40_RS17405
lldE	L-lactate dehydrogenase, LldE subunit	A6A40_RS13770
lldF	L-lactate dehydrogenase, LldF subunit	A6A40_RS13775
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	A6A40_RS10440	A6A40_RS20715
ltaE	L-threonine aldolase	A6A40_RS25640	A6A40_RS03585
lutA	L-lactate dehydrogenase, LutA subunit	A6A40_RS13770
lutB	L-lactate dehydrogenase, LutB subunit	A6A40_RS13775
lutC	L-lactate dehydrogenase, LutC subunit	A6A40_RS13780
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	A6A40_RS28250
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	A6A40_RS28245	A6A40_RS04105
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	A6A40_RS19645
pco	propanyl-CoA oxidase	A6A40_RS26290
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	A6A40_RS25400	A6A40_RS21800
prpC	2-methylcitrate synthase	A6A40_RS13735	A6A40_RS04630
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	A6A40_RS02535	A6A40_RS29930
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	A6A40_RS28270
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC	A6A40_RS16815
tdh	L-threonine 3-dehydrogenase	A6A40_RS21750	A6A40_RS13245
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	A6A40_RS14255

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.