L-threonine catabolism in Acidovorax sp. GW101-3H11

Best path

snatA, ltaE, adh, acs, gcvP, gcvT, gcvH, lpd

Also see fitness data for the top candidates

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
snatA	L-threonine transporter snatA	Ac3H11_2153	Ac3H11_817
ltaE	L-threonine aldolase	Ac3H11_4475	Ac3H11_2921
adh	acetaldehyde dehydrogenase (not acylating)	Ac3H11_4393	Ac3H11_4184
acs	acetyl-CoA synthetase, AMP-forming	Ac3H11_951	Ac3H11_191
gcvP	glycine cleavage system, P component (glycine decarboxylase)	Ac3H11_167	Ac3H11_1553
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	Ac3H11_165
gcvH	glycine cleavage system, H component (lipoyl protein)	Ac3H11_166
lpd	dihydrolipoyl dehydrogenase	Ac3H11_4091	Ac3H11_2465
Alternative steps:
ackA	acetate kinase	Ac3H11_4666
acn	(2R,3S)-2-methylcitrate dehydratase	Ac3H11_1140	Ac3H11_2323
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	Ac3H11_2323	Ac3H11_1140
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	Ac3H11_1496	Ac3H11_4393
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	Ac3H11_2396	Ac3H11_4169
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	Ac3H11_1695	Ac3H11_3210
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	Ac3H11_1694	Ac3H11_4628
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	Ac3H11_1693	Ac3H11_4983
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	Ac3H11_1692	Ac3H11_1936
D-LDH	D-lactate dehydrogenase	Ac3H11_4909	Ac3H11_2934
dddA	3-hydroxypropionate dehydrogenase	Ac3H11_3320	Ac3H11_4659
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components
epi	methylmalonyl-CoA epimerase	Ac3H11_2274
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	Ac3H11_4483	Ac3H11_4909
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	Ac3H11_3400
glcF	D-lactate dehydrogenase, FeS subunit GlcF	Ac3H11_3398
gloA	glyoxylase I	Ac3H11_2251	Ac3H11_506
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	Ac3H11_478	Ac3H11_3348
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	Ac3H11_2775	Ac3H11_4006
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	Ac3H11_4340	Ac3H11_2357
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	Ac3H11_3830
L-LDH	L-lactate dehydrogenase	Ac3H11_1623	Ac3H11_1767
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	Ac3H11_2705	Ac3H11_3189
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	Ac3H11_4483	Ac3H11_4909
lctO	L-lactate oxidase or 2-monooxygenase	Ac3H11_2838	Ac3H11_1623
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	Ac3H11_2278
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	Ac3H11_2278
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	Ac3H11_2278
pccA	propionyl-CoA carboxylase, alpha subunit	Ac3H11_2275	Ac3H11_3016
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	Ac3H11_2275	Ac3H11_4028
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	Ac3H11_2276	Ac3H11_3010
pco	propanyl-CoA oxidase	Ac3H11_3533
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	Ac3H11_2831	Ac3H11_2326
prpC	2-methylcitrate synthase	Ac3H11_2322	Ac3H11_3161
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	Ac3H11_2325	Ac3H11_4370
pta	phosphate acetyltransferase	Ac3H11_1079	Ac3H11_4331
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	Ac3H11_2042	Ac3H11_4836
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	Ac3H11_2497	Ac3H11_3163
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)

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 17 2021. The underlying query database was built on Sep 17 2021.