L-threonine catabolism in Marinobacter guineae M3B

Best path

braC, braD, braE, braF, braG, tdcB, tdcE, prpC, acnD, prpF, acn, prpB

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)	CLH62_RS07840
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	CLH62_RS07845	CLH62_RS05535
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	CLH62_RS07850	CLH62_RS05530
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	CLH62_RS07855	CLH62_RS05525
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	CLH62_RS07860	CLH62_RS05520
tdcB	L-threonine dehydratase	CLH62_RS13835	CLH62_RS12020
tdcE	2-ketobutyrate formate-lyase
prpC	2-methylcitrate synthase	CLH62_RS01920	CLH62_RS18550
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	CLH62_RS01915	CLH62_RS12705
prpF	methylaconitate isomerase	CLH62_RS01910
acn	(2R,3S)-2-methylcitrate dehydratase	CLH62_RS01915	CLH62_RS03005
prpB	2-methylisocitrate lyase	CLH62_RS01925
Alternative steps:
ackA	acetate kinase	CLH62_RS14355	CLH62_RS18460
acs	acetyl-CoA synthetase, AMP-forming	CLH62_RS16445	CLH62_RS02220
adh	acetaldehyde dehydrogenase (not acylating)	CLH62_RS14090	CLH62_RS07755
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	CLH62_RS09585	CLH62_RS09690
aldA	lactaldehyde dehydrogenase	CLH62_RS15810	CLH62_RS14090
D-LDH	D-lactate dehydrogenase	CLH62_RS09330	CLH62_RS04920
dddA	3-hydroxypropionate dehydrogenase	CLH62_RS05315	CLH62_RS11820
DVU3032	L-lactate dehydrogenase, LutC-like component	CLH62_RS06435
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	CLH62_RS09340	CLH62_RS06430
epi	methylmalonyl-CoA epimerase
gcvH	glycine cleavage system, H component (lipoyl protein)	CLH62_RS19200
gcvP	glycine cleavage system, P component (glycine decarboxylase)
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	CLH62_RS07680
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	CLH62_RS07675
glcF	D-lactate dehydrogenase, FeS subunit GlcF	CLH62_RS07670
gloA	glyoxylase I	CLH62_RS06445	CLH62_RS14925
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	CLH62_RS01225	CLH62_RS10395
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	CLH62_RS05465	CLH62_RS15970
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	CLH62_RS05310	CLH62_RS15980
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	CLH62_RS04610
L-LDH	L-lactate dehydrogenase
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	CLH62_RS00980
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	CLH62_RS06425	CLH62_RS09345
lldF	L-lactate dehydrogenase, LldF subunit	CLH62_RS06430	CLH62_RS09340
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	CLH62_RS18585	CLH62_RS03305
ltaE	L-threonine aldolase	CLH62_RS05625	CLH62_RS05965
lutA	L-lactate dehydrogenase, LutA subunit	CLH62_RS09345	CLH62_RS06425
lutB	L-lactate dehydrogenase, LutB subunit	CLH62_RS09340	CLH62_RS06430
lutC	L-lactate dehydrogenase, LutC subunit	CLH62_RS09335	CLH62_RS06435
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	CLH62_RS14370
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	CLH62_RS14385
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	CLH62_RS14370
pccA	propionyl-CoA carboxylase, alpha subunit	CLH62_RS15455	CLH62_RS04865
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	CLH62_RS13790	CLH62_RS04865
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	CLH62_RS06390
pccB	propionyl-CoA carboxylase, beta subunit	CLH62_RS15445	CLH62_RS04850
pco	propanyl-CoA oxidase	CLH62_RS10225
phtA	L-threonine uptake permease PhtA
prpD	2-methylcitrate dehydratase	CLH62_RS01880
pta	phosphate acetyltransferase	CLH62_RS18455
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	CLH62_RS14125	CLH62_RS17825
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	CLH62_RS16335	CLH62_RS07635

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.