L-threonine catabolism in Pseudomonas fluorescens FW300-N2E3

Best path

braC, braD, braE, braF, braG, ltaE, adh, ackA, pta, 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 (53 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	AO353_17125	AO353_13340
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	AO353_17120	AO353_13345
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	AO353_17115	AO353_13350
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	AO353_17110	AO353_13530
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	AO353_17105	AO353_13360
ltaE	L-threonine aldolase	AO353_07670	AO353_14020
adh	acetaldehyde dehydrogenase (not acylating)	AO353_22390	AO353_06560
ackA	acetate kinase	AO353_04410
pta	phosphate acetyltransferase	AO353_05065
gcvP	glycine cleavage system, P component (glycine decarboxylase)	AO353_03500	AO353_08720
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	AO353_03510	AO353_08735
gcvH	glycine cleavage system, H component (lipoyl protein)	AO353_08730	AO353_03495
lpd	dihydrolipoyl dehydrogenase	AO353_26650	AO353_01825
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	AO353_00890	AO353_21605
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	AO353_00890	AO353_00565
acs	acetyl-CoA synthetase, AMP-forming	AO353_03060	AO353_14365
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	AO353_19510	AO353_06560
D-LDH	D-lactate dehydrogenase	AO353_05720	AO353_02740
dddA	3-hydroxypropionate dehydrogenase	AO353_26740	AO353_07810
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	AO353_05710
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	AO353_21310
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	AO353_21305	AO353_21310
glcF	D-lactate dehydrogenase, FeS subunit GlcF	AO353_21300
gloA	glyoxylase I	AO353_26955
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	AO353_23490	AO353_16585
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	AO353_25675	AO353_24830
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	AO353_21350	AO353_06080
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	AO353_07520
L-LDH	L-lactate dehydrogenase	AO353_23830
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	AO353_01230
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	AO353_21310	AO353_08505
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	AO353_05705
lldF	L-lactate dehydrogenase, LldF subunit	AO353_05710
lldG	L-lactate dehydrogenase, LldG subunit	AO353_05715
lutA	L-lactate dehydrogenase, LutA subunit	AO353_05705
lutB	L-lactate dehydrogenase, LutB subunit	AO353_05710
lutC	L-lactate dehydrogenase, LutC subunit	AO353_05715
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	AO353_20335	AO353_19305
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	AO353_10030	AO353_13675
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	AO353_20345	AO353_19320
pco	propanyl-CoA oxidase	AO353_11100
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	AO353_00900	AO353_27735
prpC	2-methylcitrate synthase	AO353_00895	AO353_01860
prpD	2-methylcitrate dehydratase	AO353_00880
prpF	methylaconitate isomerase	AO353_00885	AO353_26715
RR42_RS28305	L-threonine:H+ symporter	AO353_16120	AO353_12275
serP1	L-threonine uptake transporter SerP1	AO353_25190	AO353_05965
snatA	L-threonine transporter snatA	AO353_13635
sstT	L-threonine:Na+ symporter SstT	AO353_20105
tdcB	L-threonine dehydratase	AO353_08485	AO353_29000
tdcC	L-threonine:H+ symporter TdcC	AO353_21595	AO353_15495
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	AO353_17425	AO353_22415
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	AO353_19655	AO353_28090

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.