L-valine catabolism in Ferroglobus placidus DSM 10642

Best path

livF, livG, livJ, livH, livM, ofoA, ofoB, 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 (25 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	FERP_RS00405	FERP_RS05240
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	FERP_RS05235	FERP_RS08410
livJ	L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)
livH	L-valine ABC transporter, permease component 1 (LivH/BraD)	FERP_RS08420
livM	L-valine ABC transporter, permease component 2 (LivM/BraE)	FERP_RS08415	FERP_RS05220
ofoA	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit OfoA	FERP_RS06455
ofoB	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit OfoB	FERP_RS06460
acdH	isobutyryl-CoA dehydrogenase	FERP_RS05015	FERP_RS09780
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	FERP_RS05170	FERP_RS09765
bch	3-hydroxyisobutyryl-CoA hydrolase	FERP_RS05170
mmsB	3-hydroxyisobutyrate dehydrogenase
mmsA	methylmalonate-semialdehyde dehydrogenase
pccA	propionyl-CoA carboxylase, alpha subunit	FERP_RS01645
pccB	propionyl-CoA carboxylase, beta subunit	FERP_RS09205
epi	methylmalonyl-CoA epimerase	FERP_RS09200
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	FERP_RS09215	FERP_RS07880
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	FERP_RS09195	FERP_RS07885
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)
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
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB
dddA	3-hydroxypropionate dehydrogenase
hpcD	3-hydroxypropionyl-CoA dehydratase	FERP_RS09765	FERP_RS05170
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	FERP_RS03895	FERP_RS07525
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	FERP_RS09215	FERP_RS07880
natA	L-valine ABC transporter, ATPase component 1 (NatA)	FERP_RS10775	FERP_RS05845
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)	FERP_RS05225
natE	L-valine ABC transporter, ATPase component 2 (NatE)	FERP_RS10770	FERP_RS05850
ofo	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	FERP_RS01645
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	FERP_RS09210	FERP_RS04900
pco	propanyl-CoA oxidase	FERP_RS07810	FERP_RS07875
phtJ	L-valine uptake permease PhtJ
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	FERP_RS04055
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	FERP_RS06455
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.