L-threonine catabolism in Azoarcus sp. BH72

Best path

snatA, 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
snatA	L-threonine transporter snatA	AZO_RS19380
ltaE	L-threonine aldolase	AZO_RS14080
adh	acetaldehyde dehydrogenase (not acylating)	AZO_RS14770	AZO_RS10715
acs	acetyl-CoA synthetase, AMP-forming	AZO_RS12180	AZO_RS08590
gcvP	glycine cleavage system, P component (glycine decarboxylase)	AZO_RS06490
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	AZO_RS06500
gcvH	glycine cleavage system, H component (lipoyl protein)	AZO_RS06495
lpd	dihydrolipoyl dehydrogenase	AZO_RS06930	AZO_RS07870
Alternative steps:
ackA	acetate kinase	AZO_RS06410	AZO_RS18270
acn	(2R,3S)-2-methylcitrate dehydratase	AZO_RS07755	AZO_RS07750
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	AZO_RS07750
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	AZO_RS12270	AZO_RS09390
aldA	lactaldehyde dehydrogenase	AZO_RS11360	AZO_RS14770
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	AZO_RS18710	AZO_RS18715
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	AZO_RS18720	AZO_RS19170
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	AZO_RS18725
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	AZO_RS18730	AZO_RS12615
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	AZO_RS18735	AZO_RS12610
D-LDH	D-lactate dehydrogenase	AZO_RS05920	AZO_RS17240
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	AZO_RS05925
epi	methylmalonyl-CoA epimerase	AZO_RS03475
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	AZO_RS05040	AZO_RS17240
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	AZO_RS05045
glcF	D-lactate dehydrogenase, FeS subunit GlcF	AZO_RS05050
gloA	glyoxylase I	AZO_RS16220	AZO_RS06195
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	AZO_RS18195	AZO_RS10375
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	AZO_RS03985	AZO_RS09740
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	AZO_RS09705	AZO_RS14770
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	AZO_RS09550
L-LDH	L-lactate dehydrogenase	AZO_RS05130	AZO_RS12460
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	AZO_RS08615	AZO_RS09710
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	AZO_RS17240	AZO_RS05040
lctO	L-lactate oxidase or 2-monooxygenase	AZO_RS03065	AZO_RS12460
lldE	L-lactate dehydrogenase, LldE subunit	AZO_RS05935
lldF	L-lactate dehydrogenase, LldF subunit	AZO_RS05925
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	AZO_RS05935
lutB	L-lactate dehydrogenase, LutB subunit	AZO_RS05925
lutC	L-lactate dehydrogenase, LutC subunit	AZO_RS05930
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	AZO_RS03440	AZO_RS03495
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	AZO_RS03440
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	AZO_RS03440	AZO_RS03495
pccA	propionyl-CoA carboxylase, alpha subunit	AZO_RS03455	AZO_RS15410
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	AZO_RS03455	AZO_RS04345
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	AZO_RS03450	AZO_RS15420
pco	propanyl-CoA oxidase	AZO_RS01635	AZO_RS09755
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	AZO_RS05675
prpC	2-methylcitrate synthase	AZO_RS07855
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	AZO_RS12825
pta	phosphate acetyltransferase	AZO_RS18265	AZO_RS16135
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	AZO_RS02520
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	AZO_RS13570	AZO_RS00560
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	AZO_RS18230

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.