L-threonine catabolism in Thauera humireducens SgZ-1

Best path

sstT, ltaE, adh, ackA, pta, 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
sstT	L-threonine:Na+ symporter SstT	AC731_RS01850
ltaE	L-threonine aldolase	AC731_RS01845	AC731_RS09830
adh	acetaldehyde dehydrogenase (not acylating)	AC731_RS10945	AC731_RS09595
ackA	acetate kinase	AC731_RS07250	AC731_RS17630
pta	phosphate acetyltransferase	AC731_RS16120	AC731_RS17635
gcvP	glycine cleavage system, P component (glycine decarboxylase)	AC731_RS07630
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	AC731_RS07620
gcvH	glycine cleavage system, H component (lipoyl protein)	AC731_RS07625
lpd	dihydrolipoyl dehydrogenase	AC731_RS01360	AC731_RS03335
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	AC731_RS03225
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)
acs	acetyl-CoA synthetase, AMP-forming	AC731_RS03990	AC731_RS19020
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	AC731_RS08900	AC731_RS01815
aldA	lactaldehyde dehydrogenase	AC731_RS17195	AC731_RS09595
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	AC731_RS15705	AC731_RS15935
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	AC731_RS15700	AC731_RS15925
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	AC731_RS15695	AC731_RS15920
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	AC731_RS17805	AC731_RS15690
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	AC731_RS15685	AC731_RS15910
D-LDH	D-lactate dehydrogenase	AC731_RS16280	AC731_RS00615
dddA	3-hydroxypropionate dehydrogenase	AC731_RS16145	AC731_RS08200
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	AC731_RS01945
epi	methylmalonyl-CoA epimerase	AC731_RS11805
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	AC731_RS04245	AC731_RS00615
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	AC731_RS04250
glcF	D-lactate dehydrogenase, FeS subunit GlcF	AC731_RS04255
gloA	glyoxylase I	AC731_RS10820	AC731_RS15835
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	AC731_RS15390	AC731_RS05600
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	AC731_RS17945	AC731_RS14145
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	AC731_RS09755	AC731_RS17195
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	AC731_RS09645
L-LDH	L-lactate dehydrogenase	AC731_RS12105
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	AC731_RS04600	AC731_RS08045
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	AC731_RS00615
lctO	L-lactate oxidase or 2-monooxygenase	AC731_RS12105
lldE	L-lactate dehydrogenase, LldE subunit	AC731_RS01940
lldF	L-lactate dehydrogenase, LldF subunit	AC731_RS01945
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	AC731_RS01940
lutB	L-lactate dehydrogenase, LutB subunit	AC731_RS01945
lutC	L-lactate dehydrogenase, LutC subunit	AC731_RS01950
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	AC731_RS11865	AC731_RS11785
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	AC731_RS11865
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	AC731_RS11865	AC731_RS11785
pccA	propionyl-CoA carboxylase, alpha subunit	AC731_RS11850	AC731_RS17125
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	AC731_RS11850	AC731_RS18430
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	AC731_RS11855	AC731_RS17115
pco	propanyl-CoA oxidase	AC731_RS10815
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	AC731_RS00035
prpC	2-methylcitrate synthase	AC731_RS03320
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	AC731_RS16785
RR42_RS28305	L-threonine:H+ symporter
serP1	L-threonine uptake transporter SerP1
snatA	L-threonine transporter snatA	AC731_RS15505
tdcB	L-threonine dehydratase	AC731_RS16610
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	AC731_RS13905	AC731_RS15395
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)

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.