L-threonine catabolism in Pandoraea thiooxydans ATSB16

Best path

braC, braD, braE, braF, braG, ltaE, adh, acs, gcvP, gcvT, gcvH, lpd

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 (54 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)	PATSB16_RS00990	PATSB16_RS12765
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	PATSB16_RS00995	PATSB16_RS05685
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	PATSB16_RS01000	PATSB16_RS05690
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	PATSB16_RS03645	PATSB16_RS05695
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	PATSB16_RS03650	PATSB16_RS12745
ltaE	L-threonine aldolase	PATSB16_RS12555	PATSB16_RS13935
adh	acetaldehyde dehydrogenase (not acylating)	PATSB16_RS15895	PATSB16_RS16135
acs	acetyl-CoA synthetase, AMP-forming	PATSB16_RS02175	PATSB16_RS15885
gcvP	glycine cleavage system, P component (glycine decarboxylase)	PATSB16_RS19560
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	PATSB16_RS19550	PATSB16_RS16185
gcvH	glycine cleavage system, H component (lipoyl protein)	PATSB16_RS19555
lpd	dihydrolipoyl dehydrogenase	PATSB16_RS05325	PATSB16_RS05810
Alternative steps:
ackA	acetate kinase	PATSB16_RS09135
acn	(2R,3S)-2-methylcitrate dehydratase	PATSB16_RS12110
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	PATSB16_RS12110
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	PATSB16_RS14005
aldA	lactaldehyde dehydrogenase	PATSB16_RS01930	PATSB16_RS15895
D-LDH	D-lactate dehydrogenase	PATSB16_RS00570	PATSB16_RS12390
dddA	3-hydroxypropionate dehydrogenase	PATSB16_RS19040	PATSB16_RS13975
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	PATSB16_RS05355	PATSB16_RS02605
epi	methylmalonyl-CoA epimerase
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	PATSB16_RS00565	PATSB16_RS03915
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	PATSB16_RS00555	PATSB16_RS03910
glcF	D-lactate dehydrogenase, FeS subunit GlcF	PATSB16_RS03905	PATSB16_RS00550
gloA	glyoxylase I	PATSB16_RS15455	PATSB16_RS17115
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	PATSB16_RS13355	PATSB16_RS19655
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	PATSB16_RS20735	PATSB16_RS06150
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	PATSB16_RS19035	PATSB16_RS01900
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	PATSB16_RS15300	PATSB16_RS16850
L-LDH	L-lactate dehydrogenase	PATSB16_RS12815
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	PATSB16_RS12955
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	PATSB16_RS00570	PATSB16_RS12390
lctO	L-lactate oxidase or 2-monooxygenase
lldE	L-lactate dehydrogenase, LldE subunit	PATSB16_RS05350	PATSB16_RS02615
lldF	L-lactate dehydrogenase, LldF subunit	PATSB16_RS02605	PATSB16_RS05355
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	PATSB16_RS02615	PATSB16_RS05350
lutB	L-lactate dehydrogenase, LutB subunit	PATSB16_RS02605	PATSB16_RS05355
lutC	L-lactate dehydrogenase, LutC subunit	PATSB16_RS02610
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	PATSB16_RS16985
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	PATSB16_RS16985
pccA	propionyl-CoA carboxylase, alpha subunit	PATSB16_RS16865	PATSB16_RS00325
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	PATSB16_RS00325	PATSB16_RS07865
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	PATSB16_RS16865
pccB	propionyl-CoA carboxylase, beta subunit	PATSB16_RS16835
pco	propanyl-CoA oxidase	PATSB16_RS19095	PATSB16_RS01745
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	PATSB16_RS10440	PATSB16_RS04010
prpC	2-methylcitrate synthase	PATSB16_RS04015	PATSB16_RS12065
prpD	2-methylcitrate dehydratase	PATSB16_RS04020
prpF	methylaconitate isomerase	PATSB16_RS19520	PATSB16_RS17580
pta	phosphate acetyltransferase	PATSB16_RS09130	PATSB16_RS13940
RR42_RS28305	L-threonine:H+ symporter	PATSB16_RS09985	PATSB16_RS06000
serP1	L-threonine uptake transporter SerP1	PATSB16_RS06000	PATSB16_RS09985
snatA	L-threonine transporter snatA	PATSB16_RS20365
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	PATSB16_RS15865	PATSB16_RS04845
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	PATSB16_RS15295	PATSB16_RS08245
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	PATSB16_RS15990	PATSB16_RS18075

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 24 2021. The underlying query database was built on Sep 17 2021.