L-threonine catabolism in Halomonas salina B6

Best path

braC, braD, braE, braF, braG, ltaE, adh, ackA, pta, 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 (51 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)	BN1003_RS00935
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BN1003_RS00925	BN1003_RS13575
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BN1003_RS00915	BN1003_RS09895
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BN1003_RS00920	BN1003_RS13585
ltaE	L-threonine aldolase	BN1003_RS01955	BN1003_RS06920
adh	acetaldehyde dehydrogenase (not acylating)	BN1003_RS06365	BN1003_RS05035
ackA	acetate kinase	BN1003_RS10595	BN1003_RS00970
pta	phosphate acetyltransferase	BN1003_RS10590	BN1003_RS00965
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BN1003_RS13990
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BN1003_RS14005	BN1003_RS05180
gcvH	glycine cleavage system, H component (lipoyl protein)	BN1003_RS13995
lpd	dihydrolipoyl dehydrogenase	BN1003_RS11195	BN1003_RS13635
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	BN1003_RS18880	BN1003_RS13220
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BN1003_RS18880	BN1003_RS08095
acs	acetyl-CoA synthetase, AMP-forming	BN1003_RS09375	BN1003_RS14720
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	BN1003_RS17970	BN1003_RS18195
D-LDH	D-lactate dehydrogenase	BN1003_RS00670	BN1003_RS05980
dddA	3-hydroxypropionate dehydrogenase	BN1003_RS10240	BN1003_RS13555
DVU3032	L-lactate dehydrogenase, LutC-like component	BN1003_RS00675
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	BN1003_RS00680
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BN1003_RS05980
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BN1003_RS05975
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BN1003_RS05970
gloA	glyoxylase I	BN1003_RS01175	BN1003_RS10755
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BN1003_RS14760	BN1003_RS09930
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	BN1003_RS18225	BN1003_RS10785
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BN1003_RS10235	BN1003_RS18710
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BN1003_RS12140
L-LDH	L-lactate dehydrogenase	BN1003_RS10110
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BN1003_RS17380
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component
lctO	L-lactate oxidase or 2-monooxygenase	BN1003_RS10110
lldE	L-lactate dehydrogenase, LldE subunit	BN1003_RS00685
lldF	L-lactate dehydrogenase, LldF subunit	BN1003_RS00680
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	BN1003_RS00685
lutB	L-lactate dehydrogenase, LutB subunit	BN1003_RS00680
lutC	L-lactate dehydrogenase, LutC subunit	BN1003_RS00675
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	BN1003_RS13665
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BN1003_RS13660	BN1003_RS14505
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BN1003_RS13665
pccA	propionyl-CoA carboxylase, alpha subunit	BN1003_RS12215	BN1003_RS16650
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BN1003_RS12215	BN1003_RS16650
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	BN1003_RS08545
pccB	propionyl-CoA carboxylase, beta subunit	BN1003_RS16635
pco	propanyl-CoA oxidase	BN1003_RS15930
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BN1003_RS18890
prpC	2-methylcitrate synthase	BN1003_RS18885	BN1003_RS11155
prpD	2-methylcitrate dehydratase	BN1003_RS18870
prpF	methylaconitate isomerase	BN1003_RS18875
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	BN1003_RS02660	BN1003_RS10165
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BN1003_RS09925	BN1003_RS18305
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	BN1003_RS10500

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.