L-valine catabolism in Lactobacillus pobuzihii E100301

Best path

bcaP, ofo, acdH, ech, bch, mmsB, mmsA, pccA, pccB, epi, mcmA

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 (18 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
bcaP	L-valine uptake transporter BcaP/CitA	LACPOB_RS0102200	LACPOB_RS0111310
ofo	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
acdH	isobutyryl-CoA dehydrogenase
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	LACPOB_RS0104330	LACPOB_RS0105745
bch	3-hydroxyisobutyryl-CoA hydrolase
mmsB	3-hydroxyisobutyrate dehydrogenase	LACPOB_RS0104540	LACPOB_RS0105710
mmsA	methylmalonate-semialdehyde dehydrogenase	LACPOB_RS0105235
pccA	propionyl-CoA carboxylase, alpha subunit	LACPOB_RS0102790	LACPOB_RS11935
pccB	propionyl-CoA carboxylase, beta subunit
epi	methylmalonyl-CoA epimerase
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)
Bap2	L-valine permease Bap2	LACPOB_RS0100170	LACPOB_RS0102155
bkdA	branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit	LACPOB_RS0104895	LACPOB_RS0105065
bkdB	branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit	LACPOB_RS0104890	LACPOB_RS0105070
bkdC	branched-chain alpha-ketoacid dehydrogenase, E2 component	LACPOB_RS0104885	LACPOB_RS0105075
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB	LACPOB_RS0103615
dddA	3-hydroxypropionate dehydrogenase
hpcD	3-hydroxypropionyl-CoA dehydratase	LACPOB_RS0104330	LACPOB_RS0105745
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	LACPOB_RS0108260	LACPOB_RS0108560
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	LACPOB_RS0103660	LACPOB_RS0111345
livH	L-valine ABC transporter, permease component 1 (LivH/BraD)
livJ	L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)
livM	L-valine ABC transporter, permease component 2 (LivM/BraE)
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	LACPOB_RS0104880	LACPOB_RS0105060
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit
natA	L-valine ABC transporter, ATPase component 1 (NatA)	LACPOB_RS0103660	LACPOB_RS0111345
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)
natE	L-valine ABC transporter, ATPase component 2 (NatE)	LACPOB_RS0106415	LACPOB_RS0108260
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	LACPOB_RS0102790	LACPOB_RS11935
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	LACPOB_RS0104340
phtJ	L-valine uptake permease PhtJ
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase
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 24 2021. The underlying query database was built on Sep 17 2021.