L-valine catabolism in Natronomonas moolapensis 8.8.11

Best path

Bap2, bkdA, bkdB, bkdC, lpd, acdH, ech, bch, mmsB, mmsA, pccA, pccB, epi, mcm-large, mcm-small

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 (28 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
Bap2	L-valine permease Bap2
bkdA	branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit	NMLP_RS06215	NMLP_RS01080
bkdB	branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit	NMLP_RS01075
bkdC	branched-chain alpha-ketoacid dehydrogenase, E2 component	NMLP_RS01070
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	NMLP_RS06160	NMLP_RS03970
acdH	isobutyryl-CoA dehydrogenase	NMLP_RS03300	NMLP_RS10135
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	NMLP_RS11070	NMLP_RS07125
bch	3-hydroxyisobutyryl-CoA hydrolase
mmsB	3-hydroxyisobutyrate dehydrogenase
mmsA	methylmalonate-semialdehyde dehydrogenase	NMLP_RS05185	NMLP_RS01965
pccA	propionyl-CoA carboxylase, alpha subunit	NMLP_RS10955
pccB	propionyl-CoA carboxylase, beta subunit	NMLP_RS10945
epi	methylmalonyl-CoA epimerase	NMLP_RS05115
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	NMLP_RS05120	NMLP_RS10125
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	NMLP_RS04825
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)
bcaP	L-valine uptake transporter BcaP/CitA
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB
dddA	3-hydroxypropionate dehydrogenase
hpcD	3-hydroxypropionyl-CoA dehydratase	NMLP_RS11070	NMLP_RS05750
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	NMLP_RS05185	NMLP_RS03525
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	NMLP_RS12685	NMLP_RS11755
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	NMLP_RS12690	NMLP_RS06805
livH	L-valine ABC transporter, permease component 1 (LivH/BraD)	NMLP_RS06815	NMLP_RS12700
livJ	L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)
livM	L-valine ABC transporter, permease component 2 (LivM/BraE)	NMLP_RS06810
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	NMLP_RS05120	NMLP_RS10125
natA	L-valine ABC transporter, ATPase component 1 (NatA)	NMLP_RS06805	NMLP_RS12690
natB	L-valine ABC transporter, substrate-binding component NatB
natC	L-valine ABC transporter, permease component 1 (NatC)
natD	L-valine ABC transporter, permease component 2 (NatD)	NMLP_RS06815
natE	L-valine ABC transporter, ATPase component 2 (NatE)	NMLP_RS06800	NMLP_RS11755
ofo	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
ofoA	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit OfoA	NMLP_RS11840
ofoB	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit OfoB	NMLP_RS11845	NMLP_RS09975
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	NMLP_RS10955
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase
phtJ	L-valine uptake permease PhtJ
prpB	2-methylisocitrate lyase	NMLP_RS06480
prpC	2-methylcitrate synthase	NMLP_RS10675
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	NMLP_RS11840
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 24 2021. The underlying query database was built on Sep 17 2021.