L-threonine catabolism in Hoeflea phototrophica DFL-43

Best path

snatA, 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 (50 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
snatA	L-threonine transporter snatA	HPDFL43_RS11225	HPDFL43_RS07640
ltaE	L-threonine aldolase	HPDFL43_RS18285	HPDFL43_RS08475
adh	acetaldehyde dehydrogenase (not acylating)	HPDFL43_RS00715	HPDFL43_RS05720
acs	acetyl-CoA synthetase, AMP-forming	HPDFL43_RS21110	HPDFL43_RS21125
gcvP	glycine cleavage system, P component (glycine decarboxylase)	HPDFL43_RS03915
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	HPDFL43_RS03925	HPDFL43_RS17155
gcvH	glycine cleavage system, H component (lipoyl protein)	HPDFL43_RS03920
lpd	dihydrolipoyl dehydrogenase	HPDFL43_RS10415	HPDFL43_RS20310
Alternative steps:
ackA	acetate kinase	HPDFL43_RS18675
acn	(2R,3S)-2-methylcitrate dehydratase	HPDFL43_RS20665
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	HPDFL43_RS20665
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	HPDFL43_RS00715	HPDFL43_RS13685
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)	HPDFL43_RS04025	HPDFL43_RS02360
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)	HPDFL43_RS04035	HPDFL43_RS00940
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	HPDFL43_RS04030	HPDFL43_RS02365
D-LDH	D-lactate dehydrogenase	HPDFL43_RS07410	HPDFL43_RS04500
dddA	3-hydroxypropionate dehydrogenase	HPDFL43_RS04230	HPDFL43_RS06720
DVU3032	L-lactate dehydrogenase, LutC-like component	HPDFL43_RS05170	HPDFL43_RS05175
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	HPDFL43_RS05175
epi	methylmalonyl-CoA epimerase	HPDFL43_RS12065
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	HPDFL43_RS05195	HPDFL43_RS04500
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	HPDFL43_RS05200
glcF	D-lactate dehydrogenase, FeS subunit GlcF	HPDFL43_RS05210
gloA	glyoxylase I	HPDFL43_RS11515	HPDFL43_RS18800
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	HPDFL43_RS16400	HPDFL43_RS19505
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	HPDFL43_RS01490	HPDFL43_RS13125
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	HPDFL43_RS11105	HPDFL43_RS04900
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	HPDFL43_RS07035	HPDFL43_RS10820
L-LDH	L-lactate dehydrogenase	HPDFL43_RS12865	HPDFL43_RS20345
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	HPDFL43_RS19405
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	HPDFL43_RS04500	HPDFL43_RS07410
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	HPDFL43_RS05180
lldF	L-lactate dehydrogenase, LldF subunit	HPDFL43_RS05175
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	HPDFL43_RS05180
lutB	L-lactate dehydrogenase, LutB subunit	HPDFL43_RS05175
lutC	L-lactate dehydrogenase, LutC subunit	HPDFL43_RS05170
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	HPDFL43_RS02410
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	HPDFL43_RS02410
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	HPDFL43_RS02410
pccA	propionyl-CoA carboxylase, alpha subunit	HPDFL43_RS02415	HPDFL43_RS15475
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	HPDFL43_RS02415	HPDFL43_RS15475
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	HPDFL43_RS15475
pccB	propionyl-CoA carboxylase, beta subunit	HPDFL43_RS02440	HPDFL43_RS15485
pco	propanyl-CoA oxidase	HPDFL43_RS13350	HPDFL43_RS14295
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	HPDFL43_RS03790	HPDFL43_RS10745
prpC	2-methylcitrate synthase	HPDFL43_RS10005	HPDFL43_RS14090
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase	HPDFL43_RS14015	HPDFL43_RS01755
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	HPDFL43_RS11885	HPDFL43_RS11000
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	HPDFL43_RS19870	HPDFL43_RS13195
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	HPDFL43_RS12945	HPDFL43_RS04890

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.