L-threonine catabolism in Jannaschia aquimarina GSW-M26

Best path

snatA, 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 (43 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
snatA	L-threonine transporter snatA	jaqu_RS01020
tdcB	L-threonine dehydratase	jaqu_RS06010	jaqu_RS13680
tdcE	2-ketobutyrate formate-lyase
pccA	propionyl-CoA carboxylase, alpha subunit	jaqu_RS11645	jaqu_RS04250
pccB	propionyl-CoA carboxylase, beta subunit	jaqu_RS11615	jaqu_RS04230
epi	methylmalonyl-CoA epimerase	jaqu_RS11880
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	jaqu_RS11670	jaqu_RS02675
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	jaqu_RS11670	jaqu_RS02675
Alternative steps:
ackA	acetate kinase	jaqu_RS11365
acn	(2R,3S)-2-methylcitrate dehydratase	jaqu_RS11455
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	jaqu_RS11455
acs	acetyl-CoA synthetase, AMP-forming	jaqu_RS18400	jaqu_RS11285
adh	acetaldehyde dehydrogenase (not acylating)	jaqu_RS08505	jaqu_RS19035
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	jaqu_RS03630	jaqu_RS08505
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	jaqu_RS04940	jaqu_RS14600
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	jaqu_RS07825
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	jaqu_RS04915	jaqu_RS14580
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	jaqu_RS04925	jaqu_RS14620
D-LDH	D-lactate dehydrogenase	jaqu_RS14480	jaqu_RS04515
dddA	3-hydroxypropionate dehydrogenase	jaqu_RS12755	jaqu_RS03625
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
gcvH	glycine cleavage system, H component (lipoyl protein)
gcvP	glycine cleavage system, P component (glycine decarboxylase)
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	jaqu_RS11125	jaqu_RS19750
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	jaqu_RS01930	jaqu_RS14480
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	jaqu_RS01935
glcF	D-lactate dehydrogenase, FeS subunit GlcF	jaqu_RS01940
gloA	glyoxylase I	jaqu_RS16715	jaqu_RS03400
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	jaqu_RS04105	jaqu_RS12255
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	jaqu_RS12650	jaqu_RS05030
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	jaqu_RS11085	jaqu_RS03630
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	jaqu_RS15850	jaqu_RS18020
L-LDH	L-lactate dehydrogenase	jaqu_RS18460	jaqu_RS02560
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	jaqu_RS01075
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	jaqu_RS01930	jaqu_RS03510
lctO	L-lactate oxidase or 2-monooxygenase	jaqu_RS18460	jaqu_RS20020
lldE	L-lactate dehydrogenase, LldE subunit
lldF	L-lactate dehydrogenase, LldF subunit
lldG	L-lactate dehydrogenase, LldG subunit
lpd	dihydrolipoyl dehydrogenase	jaqu_RS04615	jaqu_RS19795
ltaE	L-threonine aldolase	jaqu_RS01995	jaqu_RS11515
lutA	L-lactate dehydrogenase, LutA subunit
lutB	L-lactate dehydrogenase, LutB subunit
lutC	L-lactate dehydrogenase, LutC subunit
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	jaqu_RS11670	jaqu_RS02675
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	jaqu_RS11645	jaqu_RS18415
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	jaqu_RS18410
pco	propanyl-CoA oxidase	jaqu_RS05745	jaqu_RS01820
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	jaqu_RS01445
prpC	2-methylcitrate synthase	jaqu_RS06305
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	jaqu_RS11370
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
sstT	L-threonine:Na+ symporter SstT
tdcC	L-threonine:H+ symporter TdcC
tdh	L-threonine 3-dehydrogenase	jaqu_RS03420	jaqu_RS03825
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	jaqu_RS00575

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.