L-threonine catabolism in Rhodopseudomonas pseudopalustris DSM 123

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)	BMY71_RS09140
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BMY71_RS09160	BMY71_RS17340
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BMY71_RS09155	BMY71_RS17335
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BMY71_RS14870	BMY71_RS09150
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BMY71_RS09515	BMY71_RS09145
ltaE	L-threonine aldolase	BMY71_RS09070	BMY71_RS11660
adh	acetaldehyde dehydrogenase (not acylating)	BMY71_RS03050	BMY71_RS01975
acs	acetyl-CoA synthetase, AMP-forming	BMY71_RS23035	BMY71_RS06665
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BMY71_RS08915
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BMY71_RS08925
gcvH	glycine cleavage system, H component (lipoyl protein)	BMY71_RS08920
lpd	dihydrolipoyl dehydrogenase	BMY71_RS12355	BMY71_RS19260
Alternative steps:
ackA	acetate kinase	BMY71_RS04040	BMY71_RS22280
acn	(2R,3S)-2-methylcitrate dehydratase	BMY71_RS19130
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BMY71_RS19130
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	BMY71_RS01975	BMY71_RS08135
D-LDH	D-lactate dehydrogenase	BMY71_RS07015	BMY71_RS04645
dddA	3-hydroxypropionate dehydrogenase	BMY71_RS08010	BMY71_RS05955
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	BMY71_RS12670
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BMY71_RS00235	BMY71_RS07015
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BMY71_RS00230
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BMY71_RS00225
gloA	glyoxylase I	BMY71_RS18950
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BMY71_RS02245	BMY71_RS02450
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	BMY71_RS09800	BMY71_RS15005
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BMY71_RS06685	BMY71_RS03050
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BMY71_RS08615	BMY71_RS17630
L-LDH	L-lactate dehydrogenase	BMY71_RS21230	BMY71_RS19180
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	BMY71_RS03840
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BMY71_RS03845
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BMY71_RS00235	BMY71_RS07015
lctO	L-lactate oxidase or 2-monooxygenase	BMY71_RS21230
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	BMY71_RS09890
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BMY71_RS09890
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BMY71_RS09890
pccA	propionyl-CoA carboxylase, alpha subunit	BMY71_RS16270	BMY71_RS24205
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BMY71_RS16270	BMY71_RS18445
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BMY71_RS16415	BMY71_RS24200
pco	propanyl-CoA oxidase	BMY71_RS04750	BMY71_RS08460
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BMY71_RS14630	BMY71_RS16265
prpC	2-methylcitrate synthase	BMY71_RS14625	BMY71_RS12540
prpD	2-methylcitrate dehydratase	BMY71_RS14620
prpF	methylaconitate isomerase	BMY71_RS13035
pta	phosphate acetyltransferase	BMY71_RS22275	BMY71_RS04035
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	BMY71_RS15480
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BMY71_RS03650	BMY71_RS20085
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BMY71_RS16160	BMY71_RS21120

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.