L-threonine catabolism in Amycolatopsis halophila YIM 93223

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 (48 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
snatA	L-threonine transporter snatA	AMYHA_RS24790
ltaE	L-threonine aldolase	AMYHA_RS03905	AMYHA_RS04905
adh	acetaldehyde dehydrogenase (not acylating)	AMYHA_RS13095	AMYHA_RS06610
acs	acetyl-CoA synthetase, AMP-forming	AMYHA_RS05190	AMYHA_RS07525
gcvP	glycine cleavage system, P component (glycine decarboxylase)	AMYHA_RS15155
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	AMYHA_RS04895	AMYHA_RS02295
gcvH	glycine cleavage system, H component (lipoyl protein)	AMYHA_RS04900
lpd	dihydrolipoyl dehydrogenase	AMYHA_RS04850	AMYHA_RS18755
Alternative steps:
ackA	acetate kinase
acn	(2R,3S)-2-methylcitrate dehydratase	AMYHA_RS15065
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	AMYHA_RS15065
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	AMYHA_RS10790
aldA	lactaldehyde dehydrogenase	AMYHA_RS12585	AMYHA_RS25345
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	AMYHA_RS16235
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	AMYHA_RS16255	AMYHA_RS04370
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	AMYHA_RS10525	AMYHA_RS20915
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	AMYHA_RS16245	AMYHA_RS05545
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	AMYHA_RS16240	AMYHA_RS20895
D-LDH	D-lactate dehydrogenase	AMYHA_RS03205	AMYHA_RS20260
dddA	3-hydroxypropionate dehydrogenase	AMYHA_RS20340	AMYHA_RS26645
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	AMYHA_RS07735
epi	methylmalonyl-CoA epimerase	AMYHA_RS10325
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	AMYHA_RS03205	AMYHA_RS01775
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	AMYHA_RS06900
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	AMYHA_RS16070	AMYHA_RS21200
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	AMYHA_RS20710	AMYHA_RS06590
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	AMYHA_RS14120	AMYHA_RS20335
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	AMYHA_RS19530
L-LDH	L-lactate dehydrogenase	AMYHA_RS02535
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	AMYHA_RS20390
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	AMYHA_RS03205
lctO	L-lactate oxidase or 2-monooxygenase	AMYHA_RS02535
lldE	L-lactate dehydrogenase, LldE subunit	AMYHA_RS07730
lldF	L-lactate dehydrogenase, LldF subunit	AMYHA_RS07735
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	AMYHA_RS07730
lutB	L-lactate dehydrogenase, LutB subunit	AMYHA_RS07735
lutC	L-lactate dehydrogenase, LutC subunit	AMYHA_RS07740
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	AMYHA_RS25265	AMYHA_RS22150
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	AMYHA_RS25265	AMYHA_RS22150
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	AMYHA_RS25265	AMYHA_RS16400
pccA	propionyl-CoA carboxylase, alpha subunit	AMYHA_RS25215	AMYHA_RS19995
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	AMYHA_RS19995	AMYHA_RS25215
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	AMYHA_RS25160	AMYHA_RS19150
pco	propanyl-CoA oxidase	AMYHA_RS24060	AMYHA_RS09585
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	AMYHA_RS20455	AMYHA_RS10340
prpC	2-methylcitrate synthase	AMYHA_RS06260	AMYHA_RS06280
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	AMYHA_RS09030	AMYHA_RS16100
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	AMYHA_RS23285	AMYHA_RS08910
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	AMYHA_RS21240	AMYHA_RS17030

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.