L-threonine catabolism in Xanthobacter autotrophicus Py2

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 (52 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)	XAUT_RS19760	XAUT_RS07820
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	XAUT_RS19735	XAUT_RS00230
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	XAUT_RS19740	XAUT_RS20495
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	XAUT_RS04455	XAUT_RS20530
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	XAUT_RS19750	XAUT_RS04450
ltaE	L-threonine aldolase	XAUT_RS21645	XAUT_RS04355
adh	acetaldehyde dehydrogenase (not acylating)	XAUT_RS01855	XAUT_RS03370
acs	acetyl-CoA synthetase, AMP-forming	XAUT_RS07400	XAUT_RS12385
gcvP	glycine cleavage system, P component (glycine decarboxylase)	XAUT_RS11040	XAUT_RS11045
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	XAUT_RS11060	XAUT_RS04650
gcvH	glycine cleavage system, H component (lipoyl protein)	XAUT_RS11055
lpd	dihydrolipoyl dehydrogenase	XAUT_RS19705	XAUT_RS00800
Alternative steps:
ackA	acetate kinase	XAUT_RS16350
acn	(2R,3S)-2-methylcitrate dehydratase	XAUT_RS19500
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	XAUT_RS19500
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	XAUT_RS04720
aldA	lactaldehyde dehydrogenase	XAUT_RS01855	XAUT_RS16460
D-LDH	D-lactate dehydrogenase	XAUT_RS07120	XAUT_RS14210
dddA	3-hydroxypropionate dehydrogenase	XAUT_RS16315	XAUT_RS08080
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	XAUT_RS08875
epi	methylmalonyl-CoA epimerase	XAUT_RS23385
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	XAUT_RS09385	XAUT_RS07120
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	XAUT_RS09380
glcF	D-lactate dehydrogenase, FeS subunit GlcF	XAUT_RS09375
gloA	glyoxylase I	XAUT_RS21110	XAUT_RS19405
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	XAUT_RS08810	XAUT_RS10160
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	XAUT_RS04570	XAUT_RS16635
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	XAUT_RS11020	XAUT_RS16330
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	XAUT_RS10690	XAUT_RS19270
L-LDH	L-lactate dehydrogenase	XAUT_RS19880	XAUT_RS00765
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	XAUT_RS00710
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	XAUT_RS00705	XAUT_RS04640
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	XAUT_RS09385	XAUT_RS07120
lctO	L-lactate oxidase or 2-monooxygenase	XAUT_RS19880
lldE	L-lactate dehydrogenase, LldE subunit	XAUT_RS08880
lldF	L-lactate dehydrogenase, LldF subunit	XAUT_RS08875
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	XAUT_RS08880
lutB	L-lactate dehydrogenase, LutB subunit	XAUT_RS08875
lutC	L-lactate dehydrogenase, LutC subunit	XAUT_RS08870
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	XAUT_RS23975	XAUT_RS25450
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	XAUT_RS23975	XAUT_RS25435
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	XAUT_RS23975	XAUT_RS25450
pccA	propionyl-CoA carboxylase, alpha subunit	XAUT_RS23950	XAUT_RS09310
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	XAUT_RS23950	XAUT_RS17660
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	XAUT_RS23945	XAUT_RS09320
pco	propanyl-CoA oxidase	XAUT_RS23880	XAUT_RS21625
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	XAUT_RS22415
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	XAUT_RS11440
pta	phosphate acetyltransferase	XAUT_RS16345	XAUT_RS15790
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	XAUT_RS21740	XAUT_RS20780
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	XAUT_RS20420	XAUT_RS12245
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	XAUT_RS13670	XAUT_RS21540

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 Apr 09 2024. The underlying query database was built on Sep 17 2021.