L-threonine catabolism in Saccharomonospora marina XMU15

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)	SACMADRAFT_RS19825
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	SACMADRAFT_RS19805	SACMADRAFT_RS27850
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	SACMADRAFT_RS27855	SACMADRAFT_RS19810
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	SACMADRAFT_RS19815	SACMADRAFT_RS27840
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	SACMADRAFT_RS19820	SACMADRAFT_RS28595
ltaE	L-threonine aldolase	SACMADRAFT_RS27350	SACMADRAFT_RS08745
adh	acetaldehyde dehydrogenase (not acylating)	SACMADRAFT_RS11980	SACMADRAFT_RS04115
acs	acetyl-CoA synthetase, AMP-forming	SACMADRAFT_RS24615	SACMADRAFT_RS12850
gcvP	glycine cleavage system, P component (glycine decarboxylase)	SACMADRAFT_RS08730
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	SACMADRAFT_RS08735	SACMADRAFT_RS12320
gcvH	glycine cleavage system, H component (lipoyl protein)	SACMADRAFT_RS13585	SACMADRAFT_RS08740
lpd	dihydrolipoyl dehydrogenase	SACMADRAFT_RS07375	SACMADRAFT_RS07085
Alternative steps:
ackA	acetate kinase	SACMADRAFT_RS12875
acn	(2R,3S)-2-methylcitrate dehydratase	SACMADRAFT_RS13685
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	SACMADRAFT_RS13685
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	SACMADRAFT_RS13520
aldA	lactaldehyde dehydrogenase	SACMADRAFT_RS25325	SACMADRAFT_RS26445
D-LDH	D-lactate dehydrogenase	SACMADRAFT_RS06215	SACMADRAFT_RS27505
dddA	3-hydroxypropionate dehydrogenase
DVU3032	L-lactate dehydrogenase, LutC-like component
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	SACMADRAFT_RS25305
epi	methylmalonyl-CoA epimerase	SACMADRAFT_RS19220
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	SACMADRAFT_RS02295	SACMADRAFT_RS27505
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	SACMADRAFT_RS02290	SACMADRAFT_RS27505
glcF	D-lactate dehydrogenase, FeS subunit GlcF	SACMADRAFT_RS02285
gloA	glyoxylase I	SACMADRAFT_RS23730	SACMADRAFT_RS17400
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	SACMADRAFT_RS17170	SACMADRAFT_RS21720
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	SACMADRAFT_RS19140	SACMADRAFT_RS10990
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	SACMADRAFT_RS24225	SACMADRAFT_RS17745
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	SACMADRAFT_RS06865
L-LDH	L-lactate dehydrogenase	SACMADRAFT_RS06965	SACMADRAFT_RS08835
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	SACMADRAFT_RS18950	SACMADRAFT_RS09425
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	SACMADRAFT_RS21065	SACMADRAFT_RS27505
lctO	L-lactate oxidase or 2-monooxygenase	SACMADRAFT_RS08835	SACMADRAFT_RS06965
lldE	L-lactate dehydrogenase, LldE subunit	SACMADRAFT_RS25310
lldF	L-lactate dehydrogenase, LldF subunit	SACMADRAFT_RS25305
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	SACMADRAFT_RS25310	SACMADRAFT_RS02285
lutB	L-lactate dehydrogenase, LutB subunit	SACMADRAFT_RS25305
lutC	L-lactate dehydrogenase, LutC subunit	SACMADRAFT_RS25300
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	SACMADRAFT_RS04205	SACMADRAFT_RS20075
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	SACMADRAFT_RS04205	SACMADRAFT_RS20075
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	SACMADRAFT_RS04205	SACMADRAFT_RS10860
pccA	propionyl-CoA carboxylase, alpha subunit	SACMADRAFT_RS04285	SACMADRAFT_RS21155
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	SACMADRAFT_RS04285	SACMADRAFT_RS26315
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	SACMADRAFT_RS13015
pccB	propionyl-CoA carboxylase, beta subunit	SACMADRAFT_RS04305	SACMADRAFT_RS22485
pco	propanyl-CoA oxidase	SACMADRAFT_RS06025	SACMADRAFT_RS04405
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	SACMADRAFT_RS19010	SACMADRAFT_RS03145
prpC	2-methylcitrate synthase	SACMADRAFT_RS23140	SACMADRAFT_RS23100
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	SACMADRAFT_RS25120
pta	phosphate acetyltransferase
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	SACMADRAFT_RS21815	SACMADRAFT_RS07355
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	SACMADRAFT_RS11840	SACMADRAFT_RS17480
tynA	aminoacetone oxidase	SACMADRAFT_RS11755
yvgN	methylglyoxal reductase (NADPH-dependent)	SACMADRAFT_RS11215

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.