L-threonine catabolism in Rhizobium freirei PRF 81

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 (49 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)	RHSP_RS00440	RHSP_RS24770
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	RHSP_RS00465	RHSP_RS09460
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	RHSP_RS00460	RHSP_RS09455
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	RHSP_RS09470	RHSP_RS00455
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	RHSP_RS00450	RHSP_RS09465
ltaE	L-threonine aldolase	RHSP_RS13125	RHSP_RS07830
adh	acetaldehyde dehydrogenase (not acylating)	RHSP_RS24540	RHSP_RS26425
acs	acetyl-CoA synthetase, AMP-forming	RHSP_RS28970	RHSP_RS14240
gcvP	glycine cleavage system, P component (glycine decarboxylase)	RHSP_RS02990
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	RHSP_RS02980	RHSP_RS22280
gcvH	glycine cleavage system, H component (lipoyl protein)	RHSP_RS02985
lpd	dihydrolipoyl dehydrogenase	RHSP_RS25910	RHSP_RS15505
Alternative steps:
ackA	acetate kinase	RHSP_RS27420
acn	(2R,3S)-2-methylcitrate dehydratase	RHSP_RS01990
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	RHSP_RS01990
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	RHSP_RS24810	RHSP_RS32560
D-LDH	D-lactate dehydrogenase	RHSP_RS10100	RHSP_RS04905
dddA	3-hydroxypropionate dehydrogenase	RHSP_RS30985	RHSP_RS06155
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	RHSP_RS21350
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	RHSP_RS04425	RHSP_RS10100
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	RHSP_RS04430
glcF	D-lactate dehydrogenase, FeS subunit GlcF	RHSP_RS04435
gloA	glyoxylase I	RHSP_RS02660	RHSP_RS15230
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	RHSP_RS11115	RHSP_RS01225
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	RHSP_RS02715	RHSP_RS21785
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	RHSP_RS04195	RHSP_RS11840
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	RHSP_RS10935	RHSP_RS21220
L-LDH	L-lactate dehydrogenase	RHSP_RS11750	RHSP_RS01745
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	RHSP_RS26750
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	RHSP_RS26745	RHSP_RS07120
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	RHSP_RS04425	RHSP_RS04905
lctO	L-lactate oxidase or 2-monooxygenase	RHSP_RS03285	RHSP_RS11750
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	RHSP_RS01070
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	RHSP_RS01070
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	RHSP_RS01070
pccA	propionyl-CoA carboxylase, alpha subunit	RHSP_RS01065	RHSP_RS22170
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	RHSP_RS22170	RHSP_RS01065
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	RHSP_RS01060	RHSP_RS02950
pco	propanyl-CoA oxidase	RHSP_RS12310	RHSP_RS31465
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	RHSP_RS27390	RHSP_RS26785
prpC	2-methylcitrate synthase	RHSP_RS15450	RHSP_RS31540
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	RHSP_RS03525	RHSP_RS18495
RR42_RS28305	L-threonine:H+ symporter	RHSP_RS26460
serP1	L-threonine uptake transporter SerP1	RHSP_RS26460
snatA	L-threonine transporter snatA	RHSP_RS15820
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	RHSP_RS14855	RHSP_RS01490
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	RHSP_RS10930	RHSP_RS10480
tynA	aminoacetone oxidase	RHSP_RS06875
yvgN	methylglyoxal reductase (NADPH-dependent)	RHSP_RS26230	RHSP_RS07885

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.