L-threonine catabolism in Rhizobium grahamii CCGE 502

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 (47 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)	RGCCGE502_RS14505	RGCCGE502_RS13700
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	RGCCGE502_RS14530	RGCCGE502_RS20285
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	RGCCGE502_RS14525	RGCCGE502_RS20280
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	RGCCGE502_RS20295	RGCCGE502_RS14520
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	RGCCGE502_RS14515	RGCCGE502_RS20290
ltaE	L-threonine aldolase	RGCCGE502_RS25555	RGCCGE502_RS07130
adh	acetaldehyde dehydrogenase (not acylating)	RGCCGE502_RS23535	RGCCGE502_RS00735
acs	acetyl-CoA synthetase, AMP-forming	RGCCGE502_RS24205	RGCCGE502_RS24215
gcvP	glycine cleavage system, P component (glycine decarboxylase)	RGCCGE502_RS10230
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	RGCCGE502_RS10220	RGCCGE502_RS00760
gcvH	glycine cleavage system, H component (lipoyl protein)	RGCCGE502_RS10225
lpd	dihydrolipoyl dehydrogenase	RGCCGE502_RS27050	RGCCGE502_RS09015
Alternative steps:
ackA	acetate kinase	RGCCGE502_RS11645
acn	(2R,3S)-2-methylcitrate dehydratase	RGCCGE502_RS23210
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	RGCCGE502_RS23210
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	RGCCGE502_RS29515	RGCCGE502_RS14000
D-LDH	D-lactate dehydrogenase	RGCCGE502_RS12225	RGCCGE502_RS04435
dddA	3-hydroxypropionate dehydrogenase	RGCCGE502_RS28275	RGCCGE502_RS00080
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	RGCCGE502_RS07875
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	RGCCGE502_RS03955	RGCCGE502_RS12225
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	RGCCGE502_RS03960
glcF	D-lactate dehydrogenase, FeS subunit GlcF	RGCCGE502_RS03965
gloA	glyoxylase I	RGCCGE502_RS11830	RGCCGE502_RS14680
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	RGCCGE502_RS22235	RGCCGE502_RS13260
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	RGCCGE502_RS01905	RGCCGE502_RS11780
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	RGCCGE502_RS03735	RGCCGE502_RS14000
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	RGCCGE502_RS13020	RGCCGE502_RS22720
L-LDH	L-lactate dehydrogenase	RGCCGE502_RS13910	RGCCGE502_RS22935
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	RGCCGE502_RS32325
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	RGCCGE502_RS32330	RGCCGE502_RS34320
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	RGCCGE502_RS03955	RGCCGE502_RS33945
lctO	L-lactate oxidase or 2-monooxygenase	RGCCGE502_RS13910
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	RGCCGE502_RS28960
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	RGCCGE502_RS28960
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	RGCCGE502_RS28960
pccA	propionyl-CoA carboxylase, alpha subunit	RGCCGE502_RS10145	RGCCGE502_RS23990
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	RGCCGE502_RS10145	RGCCGE502_RS08095
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	RGCCGE502_RS10185	RGCCGE502_RS23995
pco	propanyl-CoA oxidase	RGCCGE502_RS31695	RGCCGE502_RS28240
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	RGCCGE502_RS03635
prpC	2-methylcitrate synthase	RGCCGE502_RS09830	RGCCGE502_RS08955
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	RGCCGE502_RS02115	RGCCGE502_RS10690
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	RGCCGE502_RS09565
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	RGCCGE502_RS08235	RGCCGE502_RS23820
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	RGCCGE502_RS13015	RGCCGE502_RS30550
tynA	aminoacetone oxidase	RGCCGE502_RS30235
yvgN	methylglyoxal reductase (NADPH-dependent)	RGCCGE502_RS23340	RGCCGE502_RS32095

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.