L-valine catabolism in Bacillus altitudinis 41KF2b

Best path

brnQ, bkdA, bkdB, bkdC, lpd, acdH, ech, bch, mmsB, mmsA, prpC, prpD, 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 (29 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB	BA79_RS07760	BA79_RS07765
bkdA	branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit	BA79_RS11115	BA79_RS01950
bkdB	branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit	BA79_RS11120	BA79_RS01105
bkdC	branched-chain alpha-ketoacid dehydrogenase, E2 component	BA79_RS11125	BA79_RS01960
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	BA79_RS01965	BA79_RS11110
acdH	isobutyryl-CoA dehydrogenase	BA79_RS09030	BA79_RS18235
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BA79_RS18210	BA79_RS07305
bch	3-hydroxyisobutyryl-CoA hydrolase	BA79_RS18210	BA79_RS08330
mmsB	3-hydroxyisobutyrate dehydrogenase	BA79_RS09935	BA79_RS01625
mmsA	methylmalonate-semialdehyde dehydrogenase	BA79_RS03900	BA79_RS04010
prpC	2-methylcitrate synthase	BA79_RS13130	BA79_RS07510
prpD	2-methylcitrate dehydratase	BA79_RS13125
acn	(2R,3S)-2-methylcitrate dehydratase	BA79_RS03665
prpB	2-methylisocitrate lyase	BA79_RS13120
Alternative steps:
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BA79_RS03665
Bap2	L-valine permease Bap2	BA79_RS05520	BA79_RS15915
bcaP	L-valine uptake transporter BcaP/CitA	BA79_RS14915	BA79_RS12440
dddA	3-hydroxypropionate dehydrogenase
epi	methylmalonyl-CoA epimerase	BA79_RS11170
hpcD	3-hydroxypropionyl-CoA dehydratase	BA79_RS07305	BA79_RS18210
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BA79_RS03900	BA79_RS13175
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	BA79_RS06410	BA79_RS10715
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	BA79_RS12885	BA79_RS05440
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)
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BA79_RS00335
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
natA	L-valine ABC transporter, ATPase component 1 (NatA)
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)	BA79_RS08570	BA79_RS11155
ofo	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
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	BA79_RS11005	BA79_RS18225
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BA79_RS18225	BA79_RS11005
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pccB	propionyl-CoA carboxylase, beta subunit	BA79_RS11175	BA79_RS18205
pco	propanyl-CoA oxidase	BA79_RS04975	BA79_RS09030
phtJ	L-valine uptake permease PhtJ
prpF	methylaconitate isomerase	BA79_RS07240
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.