L-threonine catabolism in Paraburkholderia bryophila 376MFSha3.1

Best path

braC, braD, braE, braF, braG, 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 (57 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)	H281DRAFT_02161	H281DRAFT_06096
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	H281DRAFT_04062	H281DRAFT_06397
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	H281DRAFT_04061	H281DRAFT_04452
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	H281DRAFT_02375	H281DRAFT_04060
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	H281DRAFT_06394	H281DRAFT_04059
ltaE	L-threonine aldolase	H281DRAFT_04448	H281DRAFT_04726
adh	acetaldehyde dehydrogenase (not acylating)	H281DRAFT_01117	H281DRAFT_02299
acs	acetyl-CoA synthetase, AMP-forming	H281DRAFT_04953	H281DRAFT_05523
gcvP	glycine cleavage system, P component (glycine decarboxylase)	H281DRAFT_02409
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	H281DRAFT_02411	H281DRAFT_06542
gcvH	glycine cleavage system, H component (lipoyl protein)	H281DRAFT_02410
lpd	dihydrolipoyl dehydrogenase	H281DRAFT_00468	H281DRAFT_05115
Alternative steps:
ackA	acetate kinase	H281DRAFT_00303	H281DRAFT_01409
acn	(2R,3S)-2-methylcitrate dehydratase	H281DRAFT_02981	H281DRAFT_06606
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	H281DRAFT_02981	H281DRAFT_06210
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	H281DRAFT_01665
aldA	lactaldehyde dehydrogenase	H281DRAFT_00972	H281DRAFT_03016
D-LDH	D-lactate dehydrogenase	H281DRAFT_04684	H281DRAFT_04746
dddA	3-hydroxypropionate dehydrogenase	H281DRAFT_02374	H281DRAFT_00975
DVU3032	L-lactate dehydrogenase, LutC-like component	H281DRAFT_04331
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	H281DRAFT_00473	H281DRAFT_02904
epi	methylmalonyl-CoA epimerase	H281DRAFT_04643
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	H281DRAFT_04683	H281DRAFT_04684
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	H281DRAFT_04682	H281DRAFT_04684
glcF	D-lactate dehydrogenase, FeS subunit GlcF	H281DRAFT_04681
gloA	glyoxylase I	H281DRAFT_04643
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	H281DRAFT_04399	H281DRAFT_02154
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	H281DRAFT_05725	H281DRAFT_02514
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	H281DRAFT_02373	H281DRAFT_03264
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	H281DRAFT_03587	H281DRAFT_02095
L-LDH	L-lactate dehydrogenase	H281DRAFT_05436	H281DRAFT_02928
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	H281DRAFT_04285	H281DRAFT_03367
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	H281DRAFT_04684	H281DRAFT_04480
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	H281DRAFT_02905	H281DRAFT_00472
lldF	L-lactate dehydrogenase, LldF subunit	H281DRAFT_02904	H281DRAFT_00473
lldG	L-lactate dehydrogenase, LldG subunit	H281DRAFT_02903
lutA	L-lactate dehydrogenase, LutA subunit	H281DRAFT_00472	H281DRAFT_02905
lutB	L-lactate dehydrogenase, LutB subunit	H281DRAFT_00473	H281DRAFT_02904
lutC	L-lactate dehydrogenase, LutC subunit	H281DRAFT_04331
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	H281DRAFT_01038	H281DRAFT_02110
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	H281DRAFT_01038	H281DRAFT_02076
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	H281DRAFT_02110	H281DRAFT_01038
pccA	propionyl-CoA carboxylase, alpha subunit	H281DRAFT_01343	H281DRAFT_06283
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	H281DRAFT_06283	H281DRAFT_01343
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	H281DRAFT_01345
pco	propanyl-CoA oxidase	H281DRAFT_05174	H281DRAFT_04737
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	H281DRAFT_00580	H281DRAFT_02542
prpC	2-methylcitrate synthase	H281DRAFT_06634	H281DRAFT_06327
prpD	2-methylcitrate dehydratase	H281DRAFT_06607
prpF	methylaconitate isomerase	H281DRAFT_02982	H281DRAFT_01376
pta	phosphate acetyltransferase	H281DRAFT_01410	H281DRAFT_06308
RR42_RS28305	L-threonine:H+ symporter	H281DRAFT_04042	H281DRAFT_01668
serP1	L-threonine uptake transporter SerP1	H281DRAFT_04042
snatA	L-threonine transporter snatA	H281DRAFT_05656	H281DRAFT_06268
sstT	L-threonine:Na+ symporter SstT
tdcB*	L-threonine dehydratase	H281DRAFT_01887 with H281DRAFT_04606	H281DRAFT_05256
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	H281DRAFT_03586	H281DRAFT_03803
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	H281DRAFT_00358	H281DRAFT_04096

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.