L-threonine catabolism in Rhodococcus qingshengii djl-6-2

Best path

serP1, 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 (56 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
serP1	L-threonine uptake transporter SerP1	C1M55_RS22525	C1M55_RS07700
ltaE	L-threonine aldolase	C1M55_RS28665	C1M55_RS19425
adh	acetaldehyde dehydrogenase (not acylating)	C1M55_RS09155	C1M55_RS09205
ackA	acetate kinase	C1M55_RS07470	C1M55_RS07295
pta	phosphate acetyltransferase	C1M55_RS07465
gcvP	glycine cleavage system, P component (glycine decarboxylase)	C1M55_RS16065
gcvT	glycine cleavage system, T component (tetrahydrofolate aminomethyltransferase)	C1M55_RS17795
gcvH	glycine cleavage system, H component (lipoyl protein)	C1M55_RS16090
lpd	dihydrolipoyl dehydrogenase	C1M55_RS07790	C1M55_RS25440
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	C1M55_RS15295
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	C1M55_RS15295
acs	acetyl-CoA synthetase, AMP-forming	C1M55_RS02775	C1M55_RS25270
ald-dh-CoA	acetaldehyde dehydrogenase, acylating	C1M55_RS29420	C1M55_RS04080
aldA	lactaldehyde dehydrogenase	C1M55_RS09205	C1M55_RS09155
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	C1M55_RS16620
braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	C1M55_RS16600	C1M55_RS07895
braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	C1M55_RS16605	C1M55_RS22585
braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	C1M55_RS16610	C1M55_RS22600
braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	C1M55_RS16615	C1M55_RS06875
D-LDH	D-lactate dehydrogenase	C1M55_RS25910	C1M55_RS29255
dddA	3-hydroxypropionate dehydrogenase	C1M55_RS09145
DVU3032	L-lactate dehydrogenase, LutC-like component	C1M55_RS26545
DVU3033	L-lactate dehydrogenase, fused LutA/LutB components	C1M55_RS26550
epi	methylmalonyl-CoA epimerase	C1M55_RS19315	C1M55_RS04095
glcD	D-lactate dehydrogenase, FAD-linked subunit 1 (GlcD)	C1M55_RS14080	C1M55_RS00120
glcE	D-lactate dehydrogenase, FAD-linked subunit 2 (GlcE)	C1M55_RS14080	C1M55_RS25910
glcF	D-lactate dehydrogenase, FeS subunit GlcF
gloA	glyoxylase I
gloB	hydroxyacylglutathione hydrolase (glyoxalase II)	C1M55_RS14620	C1M55_RS27570
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	C1M55_RS19610	C1M55_RS01960
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	C1M55_RS19630	C1M55_RS10170
kbl	glycine C-acetyltransferase (2-amino-3-ketobutyrate CoA-ligase)	C1M55_RS17250
L-LDH	L-lactate dehydrogenase	C1M55_RS20815	C1M55_RS09110
lctB	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), small subunit	C1M55_RS12385
lctC	electron-transfer flavoprotein for D-lactate dehydrogenase (NAD+, ferredoxin), large subunit	C1M55_RS12390
lctD	D-lactate dehydrogenase (NAD+, ferredoxin), lactate dehydrogenase component	C1M55_RS20235	C1M55_RS25910
lctO	L-lactate oxidase or 2-monooxygenase	C1M55_RS01325	C1M55_RS09110
lldE	L-lactate dehydrogenase, LldE subunit	C1M55_RS26555
lldF	L-lactate dehydrogenase, LldF subunit	C1M55_RS26550
lldG	L-lactate dehydrogenase, LldG subunit
lutA	L-lactate dehydrogenase, LutA subunit	C1M55_RS26555
lutB	L-lactate dehydrogenase, LutB subunit	C1M55_RS26550
lutC	L-lactate dehydrogenase, LutC subunit	C1M55_RS26545
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	C1M55_RS15405
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	C1M55_RS15405
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	C1M55_RS15405	C1M55_RS15400
pccA	propionyl-CoA carboxylase, alpha subunit	C1M55_RS10790	C1M55_RS09265
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	C1M55_RS09265	C1M55_RS10790
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	C1M55_RS09265
pccB	propionyl-CoA carboxylase, beta subunit	C1M55_RS10840	C1M55_RS01140
pco	propanyl-CoA oxidase	C1M55_RS08415	C1M55_RS24690
phtA	L-threonine uptake permease PhtA
prpB	2-methylisocitrate lyase	C1M55_RS07975	C1M55_RS25470
prpC	2-methylcitrate synthase	C1M55_RS25465	C1M55_RS23230
prpD	2-methylcitrate dehydratase	C1M55_RS25475
prpF	methylaconitate isomerase
RR42_RS28305	L-threonine:H+ symporter	C1M55_RS22525	C1M55_RS07700
snatA	L-threonine transporter snatA	C1M55_RS20405
sstT	L-threonine:Na+ symporter SstT
tdcB	L-threonine dehydratase	C1M55_RS17365	C1M55_RS21040
tdcC	L-threonine:H+ symporter TdcC
tdcE	2-ketobutyrate formate-lyase
tdh	L-threonine 3-dehydrogenase	C1M55_RS09025	C1M55_RS08995
tynA	aminoacetone oxidase
yvgN	methylglyoxal reductase (NADPH-dependent)	C1M55_RS22915	C1M55_RS04335

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.