L-threonine catabolism in Burkholderia phytofirmans PsJN

Best path

snatA, 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 (58 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
snatA	L-threonine transporter snatA	BPHYT_RS17695
ltaE	L-threonine aldolase	BPHYT_RS13965	BPHYT_RS29600
adh	acetaldehyde dehydrogenase (not acylating)	BPHYT_RS25810	BPHYT_RS00120
ackA	acetate kinase	BPHYT_RS06125	BPHYT_RS26200
pta	phosphate acetyltransferase	BPHYT_RS21700	BPHYT_RS27695
gcvP	glycine cleavage system, P component (glycine decarboxylase)	BPHYT_RS19330
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	BPHYT_RS19320	BPHYT_RS24765
gcvH	glycine cleavage system, H component (lipoyl protein)	BPHYT_RS19325
lpd	dihydrolipoyl dehydrogenase	BPHYT_RS12830	BPHYT_RS08120
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	BPHYT_RS30145	BPHYT_RS10160
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BPHYT_RS30145	BPHYT_RS33980
acs	acetyl-CoA synthetase, AMP-forming	BPHYT_RS07000	BPHYT_RS27780
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	BPHYT_RS07245	BPHYT_RS21770
aldA	lactaldehyde dehydrogenase	BPHYT_RS09875	BPHYT_RS09900
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	BPHYT_RS01885	BPHYT_RS26525
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	BPHYT_RS15605	BPHYT_RS31740
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	BPHYT_RS31745	BPHYT_RS15600
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	BPHYT_RS15595	BPHYT_RS31750
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	BPHYT_RS15590	BPHYT_RS31755
D-LDH	D-lactate dehydrogenase	BPHYT_RS03515	BPHYT_RS03835
dddA	3-hydroxypropionate dehydrogenase	BPHYT_RS19495	BPHYT_RS21745
DVU3032	L-lactate dehydrogenase, LutC-like component	BPHYT_RS14530
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	BPHYT_RS12805	BPHYT_RS26970
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	BPHYT_RS31645	BPHYT_RS03510
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	BPHYT_RS31650	BPHYT_RS03505
glcF	D-lactate dehydrogenase, FeS subunit GlcF	BPHYT_RS31655	BPHYT_RS03500
gloA	glyoxylase I	BPHYT_RS03320	BPHYT_RS22605
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	BPHYT_RS14210	BPHYT_RS00495
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	BPHYT_RS25360	BPHYT_RS17335
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BPHYT_RS19500	BPHYT_RS28825
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	BPHYT_RS34655	BPHYT_RS02160
L-LDH	L-lactate dehydrogenase	BPHYT_RS31690	BPHYT_RS27110
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	BPHYT_RS20830	BPHYT_RS14800
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	BPHYT_RS31645	BPHYT_RS03515
lctO	L-lactate oxidase or 2-monooxygenase	BPHYT_RS31690
lldE	L-lactate dehydrogenase, LldE subunit	BPHYT_RS26975	BPHYT_RS12810
lldF	L-lactate dehydrogenase, LldF subunit	BPHYT_RS26970	BPHYT_RS12805
lldG	L-lactate dehydrogenase, LldG subunit	BPHYT_RS26965
lutA	L-lactate dehydrogenase, LutA subunit	BPHYT_RS12810	BPHYT_RS26975
lutB	L-lactate dehydrogenase, LutB subunit	BPHYT_RS12805	BPHYT_RS26970
lutC	L-lactate dehydrogenase, LutC subunit	BPHYT_RS14530
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	BPHYT_RS02085
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BPHYT_RS02305
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BPHYT_RS02085
pccA	propionyl-CoA carboxylase, alpha subunit	BPHYT_RS23275	BPHYT_RS17015
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BPHYT_RS17015	BPHYT_RS25975
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BPHYT_RS23265
pco	propanyl-CoA oxidase	BPHYT_RS11475	BPHYT_RS03780
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	BPHYT_RS12285	BPHYT_RS26855
prpC	2-methylcitrate synthase	BPHYT_RS33965	BPHYT_RS30150
prpD	2-methylcitrate dehydratase	BPHYT_RS33975
prpF	methylaconitate isomerase	BPHYT_RS30140	BPHYT_RS27420
RR42_RS28305	L-threonine:H+ symporter	BPHYT_RS15500	BPHYT_RS07280
serP1	L-threonine uptake transporter SerP1	BPHYT_RS15500	BPHYT_RS21680
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	BPHYT_RS03145	BPHYT_RS11065
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	BPHYT_RS34650	BPHYT_RS20205
tynA	aminoacetone oxidase	BPHYT_RS09910
yvgN	methylglyoxal reductase (NADPH-dependent)	BPHYT_RS08410	BPHYT_RS15795

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.