L-threonine catabolism in Pseudomonas fluorescens FW300-N2C3

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)	AO356_05320	AO356_08500
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	AO356_05325	AO356_08495
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	AO356_05330	AO356_08490
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	AO356_05335	AO356_29020
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	AO356_05340	AO356_08480
ltaE	L-threonine aldolase	AO356_13955	AO356_15725
adh	acetaldehyde dehydrogenase (not acylating)	AO356_28025	AO356_15225
ackA	acetate kinase	AO356_17605
pta	phosphate acetyltransferase	AO356_16680
gcvP	glycine cleavage system, P component (glycine decarboxylase)	AO356_18170
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	AO356_18160	AO356_13035
gcvH	glycine cleavage system, H component (lipoyl protein)	AO356_13040	AO356_18175
lpd	dihydrolipoyl dehydrogenase	AO356_22975	AO356_19705
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	AO356_20875	AO356_24390
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	AO356_20875	AO356_02385
acs	acetyl-CoA synthetase, AMP-forming	AO356_18695	AO356_16045
ald-dh-CoA	acetaldehyde dehydrogenase, acylating
aldA	lactaldehyde dehydrogenase	AO356_26145	AO356_28685
D-LDH	D-lactate dehydrogenase	AO356_07570	AO356_19040
dddA	3-hydroxypropionate dehydrogenase	AO356_21730	AO356_30225
DVU3032	L-lactate dehydrogenase, LutC-like component	AO356_07560
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	AO356_07560
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	AO356_01090	AO356_24000
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	AO356_01095
glcF	D-lactate dehydrogenase, FeS subunit GlcF	AO356_01100
gloA	glyoxylase I	AO356_22815
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	AO356_24480	AO356_05915
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	AO356_26360	AO356_30355
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	AO356_23175	AO356_07950
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	AO356_14140
L-LDH	L-lactate dehydrogenase	AO356_26080
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	AO356_20325	AO356_21850
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	AO356_01090	AO356_24000
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	AO356_07555
lldF	L-lactate dehydrogenase, LldF subunit	AO356_07560
lldG	L-lactate dehydrogenase, LldG subunit	AO356_07565
lutA	L-lactate dehydrogenase, LutA subunit	AO356_07555
lutB	L-lactate dehydrogenase, LutB subunit	AO356_07560
lutC	L-lactate dehydrogenase, LutC subunit	AO356_07565
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	AO356_01595	AO356_02930
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	AO356_12020	AO356_08195
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	AO356_01585	AO356_02920
pco	propanyl-CoA oxidase	AO356_10850	AO356_26355
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	AO356_20865	AO356_22080
prpC	2-methylcitrate synthase	AO356_20870	AO356_19670
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	AO356_20880	AO356_28890
RR42_RS28305	L-threonine:H+ symporter	AO356_17670	AO356_18530
serP1	L-threonine uptake transporter SerP1	AO356_29455	AO356_18530
snatA	L-threonine transporter snatA	AO356_08255
sstT	L-threonine:Na+ symporter SstT	AO356_01815
tdcB	L-threonine dehydratase	AO356_10330	AO356_27710
tdcC	L-threonine:H+ symporter TdcC	AO356_24385
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	AO356_04765	AO356_28020
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	AO356_01320

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.