L-valine catabolism in Algiphilus aromaticivorans DG1253

Best path

Bap2, ofo, acdH, ech, bch, mmsB, mmsA, prpC, acnD, prpF, acn, prpB

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
ofo	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
acdH	isobutyryl-CoA dehydrogenase	U743_RS11515	U743_RS12745
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	U743_RS08020	U743_RS10200
bch	3-hydroxyisobutyryl-CoA hydrolase	U743_RS10200	U743_RS02455
mmsB	3-hydroxyisobutyrate dehydrogenase	U743_RS16520
mmsA	methylmalonate-semialdehyde dehydrogenase	U743_RS02990	U743_RS16355
prpC	2-methylcitrate synthase	U743_RS01515	U743_RS00135
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	U743_RS05220	U743_RS06915
prpF	methylaconitate isomerase	U743_RS05215
acn	(2R,3S)-2-methylcitrate dehydratase	U743_RS05220	U743_RS06915
prpB	2-methylisocitrate lyase	U743_RS06375	U743_RS01510
Alternative steps:
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	U743_RS01445	U743_RS06460
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB
dddA	3-hydroxypropionate dehydrogenase	U743_RS16290
epi	methylmalonyl-CoA epimerase
hpcD	3-hydroxypropionyl-CoA dehydratase	U743_RS10200	U743_RS02455
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	U743_RS16355	U743_RS02990
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	U743_RS13640	U743_RS02465
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	U743_RS02465	U743_RS13635
livH	L-valine ABC transporter, permease component 1 (LivH/BraD)	U743_RS13625
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	U743_RS06470	U743_RS05580
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	U743_RS05565
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	U743_RS05565	U743_RS15540
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	U743_RS05565
natA	L-valine ABC transporter, ATPase component 1 (NatA)	U743_RS02465	U743_RS13635
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)	U743_RS13640	U743_RS02465
ofoA	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit OfoA
ofoB	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit OfoB
pccA	propionyl-CoA carboxylase, alpha subunit	U743_RS04860	U743_RS12090
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	U743_RS12090	U743_RS04860
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	U743_RS03400	U743_RS04850
pco	propanyl-CoA oxidase	U743_RS09010
phtJ	L-valine uptake permease PhtJ
prpD	2-methylcitrate dehydratase	U743_RS13225
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.