L-valine catabolism in Dechlorosoma suillum PS

Best path

livF, livG, livJ, livH, livM, ofo, acdH, ech, bch, mmsB, mmsA, pccA, pccB, epi, mcm-large, mcm-small

Also see fitness data for the top candidates

Rules

Overview: Valine degradation in GapMind is based on MetaCyc pathway L-valine degradation I (link). The other pathways do not produce any fixed carbon and are not included.

• all: valine-transport, BKD, acdH, ech, bch, mmsB, mmsA and propionyl-CoA-degradation
  • Comment: An aminotransferase (not represented) forms 3-methyl-2-oxobutanoate, the decarboxylating alpha-ketoacid dehydrogenase (BKD) forms isobutanoyl-CoA, dehydrogenase acdH forms methylacrylyl-CoA (2-methylprop-2-enoyl-CoA), the hydratase ech forms (S)-3-hydroxy-isobutaonoyl-CoA, a hydrolase forms (S)-3-hydroxy-isobutanoate, a dehydrogenase forms (S)-methylmalonate semialdehyde (2-methyl-3-oxopropanoate), and a decarboxylating dehydrogenase forms propionyl-CoA.
• BKD:
  • bkdA, bkdB, bkdC and lpd
  • or vorA, vorB and vorC
  • or ofoA and ofoB
  • or ofo
  • Comment: These decarboxylating dehydrogenases act on 4-methyl-2-oxopentanoate, 3-methyl-2-oxobutanoate (2-oxoisovalerate) and (S)-3-methyl-2-oxopentanoate and are known as the branched-chain alpha-ketoacid dehydrogenases. They can pass electrons to NAD (EC 1.2.1.25) or to ferredoxin (EC 1.2.7.7). The NAD-dependent enzyme is the sum of three activities: EC 1.2.4.4 (the 4-methyl-2-oxopentanoate dehydrogenase, with transfer to the lipopoyllysine residue of 2.3.1.168) which is itself heteromeric, with alpha and beta subunits; EC 2.3.1.168 (dihydrolipoyllysine-residue (3-methylbutanoyl)transferase); and EC 1.8.1.4 (dihydrolipoyl dehydrogenase, transferring electrons to NAD). The well-characterized ferredoxin-dependent enzymes have 3 subunits (vorABC) or 2 subunits (ofoAB). Genetic data identified a fused ferredoxin-dependent enzyme with just 1 subunit (ofo).
• 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.
• valine-transport:
  • livF, livG, livJ, livH and livM
  • or natA, natB, natC, natD and natE
  • or Bap2
  • or brnQ
  • or phtJ
  • or bcaP
  • Comment: Transporters were identified using query: transporter:valine:L-valine:val

47 steps (31 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	Dsui_2057	Dsui_0626
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	Dsui_2058	Dsui_0627
livJ	L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)	Dsui_0630	Dsui_2061
livH	L-valine ABC transporter, permease component 1 (LivH/BraD)	Dsui_0629	Dsui_2060
livM	L-valine ABC transporter, permease component 2 (LivM/BraE)	Dsui_0628	Dsui_2059
ofo	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused	Dsui_0379
acdH	isobutyryl-CoA dehydrogenase	Dsui_0977	Dsui_0975
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	Dsui_1378	Dsui_0323
bch	3-hydroxyisobutyryl-CoA hydrolase	Dsui_1378	Dsui_0981
mmsB	3-hydroxyisobutyrate dehydrogenase	Dsui_3436	Dsui_3438
mmsA	methylmalonate-semialdehyde dehydrogenase	Dsui_0437	Dsui_0105
pccA	propionyl-CoA carboxylase, alpha subunit	Dsui_0516	Dsui_0982
pccB	propionyl-CoA carboxylase, beta subunit	Dsui_0517	Dsui_0980
epi	methylmalonyl-CoA epimerase	Dsui_0512
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	Dsui_0519	Dsui_1105
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	Dsui_0519
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	Dsui_2205	Dsui_2347
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	Dsui_2347
Bap2	L-valine permease Bap2
bcaP	L-valine uptake transporter BcaP/CitA
bkdA	branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit
bkdB	branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit
bkdC	branched-chain alpha-ketoacid dehydrogenase, E2 component	Dsui_1577	Dsui_2218
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB
dddA	3-hydroxypropionate dehydrogenase
hpcD	3-hydroxypropionyl-CoA dehydratase	Dsui_1378	Dsui_0521
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	Dsui_0437	Dsui_0105
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	Dsui_1576	Dsui_2219
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	Dsui_0519	Dsui_1105
natA	L-valine ABC transporter, ATPase component 1 (NatA)	Dsui_2058	Dsui_0627
natB	L-valine ABC transporter, substrate-binding component NatB
natC	L-valine ABC transporter, permease component 1 (NatC)	Dsui_0628
natD	L-valine ABC transporter, permease component 2 (NatD)	Dsui_0629	Dsui_2060
natE	L-valine ABC transporter, ATPase component 2 (NatE)	Dsui_0841	Dsui_2057
ofoA	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit OfoA
ofoB	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit OfoB
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	Dsui_0516	Dsui_0389
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	Dsui_1637	Dsui_3369
phtJ	L-valine uptake permease PhtJ
prpB	2-methylisocitrate lyase	Dsui_0011
prpC	2-methylcitrate synthase	Dsui_2216
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
vorA	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit VorA
vorB	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit VorB
vorC	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, gamma subunit VorC

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 17 2021. The underlying query database was built on Sep 17 2021.