L-threonine catabolism in Amycolatopsis xylanica CPCC 202699

Best path

RR42_RS28305, 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 (45 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
RR42_RS28305	L-threonine:H+ symporter	BLV57_RS32970	BLV57_RS35065
ltaE	L-threonine aldolase	BLV57_RS11205	BLV57_RS35120
adh	acetaldehyde dehydrogenase (not acylating)	BLV57_RS05155	BLV57_RS28715
acs	acetyl-CoA synthetase, AMP-forming	BLV57_RS09725	BLV57_RS31585
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BLV57_RS03145	BLV57_RS35105
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BLV57_RS35110	BLV57_RS17145
gcvH	glycine cleavage system, H component (lipoyl protein)	BLV57_RS03115	BLV57_RS35115
lpd	dihydrolipoyl dehydrogenase	BLV57_RS29630	BLV57_RS41645
Alternative steps:
ackA	acetate kinase	BLV57_RS03855
acn	(2R,3S)-2-methylcitrate dehydratase	BLV57_RS03260
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BLV57_RS03260
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	BLV57_RS32000
aldA	lactaldehyde dehydrogenase	BLV57_RS02060	BLV57_RS28715
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)	BLV57_RS38615
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BLV57_RS38610	BLV57_RS05265
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BLV57_RS38605	BLV57_RS30165
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BLV57_RS38600	BLV57_RS30160
D-LDH	D-lactate dehydrogenase	BLV57_RS33080	BLV57_RS11550
dddA	3-hydroxypropionate dehydrogenase	BLV57_RS10945	BLV57_RS16295
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	BLV57_RS14775
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BLV57_RS11550
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BLV57_RS11550
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	BLV57_RS08860
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BLV57_RS01695	BLV57_RS17650
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	BLV57_RS35310	BLV57_RS20495
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BLV57_RS35960	BLV57_RS21830
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BLV57_RS37650	BLV57_RS07280
L-LDH	L-lactate dehydrogenase	BLV57_RS41370	BLV57_RS29960
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BLV57_RS35545
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BLV57_RS11550
lctO	L-lactate oxidase or 2-monooxygenase	BLV57_RS29960	BLV57_RS41370
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	BLV57_RS28865	BLV57_RS15930
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BLV57_RS28865	BLV57_RS15930
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BLV57_RS28865	BLV57_RS23065
pccA	propionyl-CoA carboxylase, alpha subunit	BLV57_RS28975	BLV57_RS16770
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BLV57_RS28975	BLV57_RS13960
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BLV57_RS29030	BLV57_RS36630
pco	propanyl-CoA oxidase	BLV57_RS17700	BLV57_RS20510
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BLV57_RS35445	BLV57_RS03460
prpC	2-methylcitrate synthase	BLV57_RS07895	BLV57_RS08055
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
pta	phosphate acetyltransferase
serP1	L-threonine uptake transporter SerP1	BLV57_RS32970	BLV57_RS35065
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	BLV57_RS16455	BLV57_RS17780
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BLV57_RS37655	BLV57_RS21115
tynA	aminoacetone oxidase	BLV57_RS05245
yvgN	methylglyoxal reductase (NADPH-dependent)	BLV57_RS22620	BLV57_RS25750

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.