L-threonine catabolism in Halomonas titanicae BH1

Best path

sstT, 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 (45 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
sstT	L-threonine:Na+ symporter SstT	HALTITAN_RS21385
ltaE	L-threonine aldolase	HALTITAN_RS15350	HALTITAN_RS10865
adh	acetaldehyde dehydrogenase (not acylating)	HALTITAN_RS12875	HALTITAN_RS00625
ackA	acetate kinase	HALTITAN_RS11380
pta	phosphate acetyltransferase	HALTITAN_RS11375
gcvP	glycine cleavage system, P component (glycine decarboxylase)	HALTITAN_RS06980
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	HALTITAN_RS06995	HALTITAN_RS01505
gcvH	glycine cleavage system, H component (lipoyl protein)	HALTITAN_RS06985
lpd	dihydrolipoyl dehydrogenase	HALTITAN_RS12210	HALTITAN_RS09625
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	HALTITAN_RS18475	HALTITAN_RS09135
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	HALTITAN_RS18475	HALTITAN_RS14545
acs	acetyl-CoA synthetase, AMP-forming	HALTITAN_RS13325	HALTITAN_RS16970
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	HALTITAN_RS23055	HALTITAN_RS00660
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	HALTITAN_RS19895
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	HALTITAN_RS19880	HALTITAN_RS02320
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)	HALTITAN_RS19870	HALTITAN_RS02310
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	HALTITAN_RS19875	HALTITAN_RS02305
D-LDH	D-lactate dehydrogenase	HALTITAN_RS03140	HALTITAN_RS13950
dddA	3-hydroxypropionate dehydrogenase	HALTITAN_RS21330	HALTITAN_RS05605
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	HALTITAN_RS13180	HALTITAN_RS07515
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	HALTITAN_RS13185	HALTITAN_RS02510
glcF	D-lactate dehydrogenase, FeS subunit GlcF	HALTITAN_RS13190
gloA	glyoxylase I	HALTITAN_RS19585	HALTITAN_RS22710
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	HALTITAN_RS16930	HALTITAN_RS24220
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	HALTITAN_RS11900	HALTITAN_RS01660
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	HALTITAN_RS21335	HALTITAN_RS00495
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	HALTITAN_RS21760	HALTITAN_RS21140
L-LDH	L-lactate dehydrogenase	HALTITAN_RS23960	HALTITAN_RS22490
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	HALTITAN_RS23340	HALTITAN_RS04845
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	HALTITAN_RS02510
lctO	L-lactate oxidase or 2-monooxygenase	HALTITAN_RS23960	HALTITAN_RS22490
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
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
pccA	propionyl-CoA carboxylase, alpha subunit	HALTITAN_RS05140	HALTITAN_RS06100
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	HALTITAN_RS06100	HALTITAN_RS02185
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	HALTITAN_RS07915
pccB	propionyl-CoA carboxylase, beta subunit	HALTITAN_RS05150
pco	propanyl-CoA oxidase	HALTITAN_RS07760	HALTITAN_RS16815
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	HALTITAN_RS18465
prpC	2-methylcitrate synthase	HALTITAN_RS18470	HALTITAN_RS12175
prpD	2-methylcitrate dehydratase	HALTITAN_RS18485
prpF	methylaconitate isomerase	HALTITAN_RS18480
RR42_RS28305	L-threonine:H+ symporter	HALTITAN_RS15020
serP1	L-threonine uptake transporter SerP1	HALTITAN_RS15020
snatA	L-threonine transporter snatA
tdcB	L-threonine dehydratase	HALTITAN_RS04435
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	HALTITAN_RS24135	HALTITAN_RS21835
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	HALTITAN_RS11075	HALTITAN_RS11585

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.