L-threonine catabolism in Shewanella sp. ANA-3

Best path

sstT, 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 (42 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
sstT	L-threonine:Na+ symporter SstT	Shewana3_1426
ltaE	L-threonine aldolase	Shewana3_1208	Shewana3_1094
adh	acetaldehyde dehydrogenase (not acylating)	Shewana3_0250	Shewana3_1788
ackA	acetate kinase	Shewana3_1552	Shewana3_3197
pta	phosphate acetyltransferase	Shewana3_1551
gcvP	glycine cleavage system, P component (glycine decarboxylase)	Shewana3_3499
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	Shewana3_3501
gcvH	glycine cleavage system, H component (lipoyl protein)	Shewana3_3500
lpd	dihydrolipoyl dehydrogenase	Shewana3_0428	Shewana3_4345
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	Shewana3_3827	Shewana3_0433
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	Shewana3_3827
acs	acetyl-CoA synthetase, AMP-forming	Shewana3_2523	Shewana3_1675
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	Shewana3_1788
aldA	lactaldehyde dehydrogenase	Shewana3_3105	Shewana3_0250
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	Shewana3_0673	Shewana3_1620
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	Shewana3_0673	Shewana3_0880
D-LDH	D-lactate dehydrogenase	Shewana3_2905	Shewana3_3319
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component	Shewana3_2908
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	Shewana3_2907
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I	Shewana3_2232	Shewana3_2721
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	Shewana3_2369	Shewana3_1493
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	Shewana3_2768	Shewana3_1461
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	Shewana3_3107	Shewana3_2770
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	Shewana3_4104	Shewana3_2518
L-LDH	L-lactate dehydrogenase
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	Shewana3_1406
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	Shewana3_2906
lldF	L-lactate dehydrogenase, LldF subunit	Shewana3_2907
lldG	L-lactate dehydrogenase, LldG subunit	Shewana3_2908
lutA	L-lactate dehydrogenase, LutA subunit	Shewana3_2906
lutB	L-lactate dehydrogenase, LutB subunit	Shewana3_2907
lutC	L-lactate dehydrogenase, LutC subunit
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	Shewana3_1669	Shewana3_3438
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	Shewana3_1669	Shewana3_3438
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	Shewana3_1671
pco	propanyl-CoA oxidase
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	Shewana3_3825	Shewana3_2942
prpC	2-methylcitrate synthase	Shewana3_3826	Shewana3_1705
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	Shewana3_3828
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	Shewana3_1789
tdcB	L-threonine dehydratase	Shewana3_0359
tdcC	L-threonine:H+ symporter TdcC	Shewana3_3365
tdcE	2-ketobutyrate formate-lyase	Shewana3_1555
tdh	L-threonine 3-dehydrogenase	Shewana3_4105	Shewana3_2938
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	Shewana3_3599

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.