L-valine catabolism in Sinorhizobium meliloti 1021

Best path

livF, livG, livJ, livH, livM, bkdA, bkdB, bkdC, lpd, acdH, ech, bch, mmsB, mmsA, pccA, pccB, epi, mcm-large, mcm-small

Also see fitness data for the top candidates

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 (34 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	SMc01948	SMc02358
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	SMc01949	SMc02357
livJ	L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)	SMc01946	SMc00078
livH	L-valine ABC transporter, permease component 1 (LivH/BraD)	SMc01951	SMc02359
livM	L-valine ABC transporter, permease component 2 (LivM/BraE)	SMc01950
bkdA	branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit	SMc03201	SMc01030
bkdB	branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit	SMc03202	SM_b20020
bkdC	branched-chain alpha-ketoacid dehydrogenase, E2 component	SMc03203	SM_b20019
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	SMc03204	SMc01035
acdH	isobutyryl-CoA dehydrogenase	SM_b20753	SMa1400
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	SMc01153	SMc01669
bch	3-hydroxyisobutyryl-CoA hydrolase	SM_b20752	SMc01669
mmsB	3-hydroxyisobutyrate dehydrogenase	SM_b20751	SMc00274
mmsA	methylmalonate-semialdehyde dehydrogenase	SMc00781	SMc00094
pccA	propionyl-CoA carboxylase, alpha subunit	SM_b20756	SM_b21124
pccB	propionyl-CoA carboxylase, beta subunit	SM_b20755	SM_b21122
epi	methylmalonyl-CoA epimerase	SMc01930
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	SM_b20757
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	SM_b20757
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	SMc03846
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	SMc03846
Bap2	L-valine permease Bap2
bcaP	L-valine uptake transporter BcaP/CitA
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB
dddA	3-hydroxypropionate dehydrogenase	SMc03116	SM_b20496
hpcD	3-hydroxypropionyl-CoA dehydratase	SMc01153	SMc04398
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	SMc00781	SM_b20891
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	SM_b20757
natA	L-valine ABC transporter, ATPase component 1 (NatA)	SMc03120	SMc01949
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)	SM_b20604
natE	L-valine ABC transporter, ATPase component 2 (NatE)	SMc01948	SMc02358
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
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	SM_b20756	SMc01345
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	SMc03895
pco	propanyl-CoA oxidase	SM_b21181	SM_b21121
phtJ	L-valine uptake permease PhtJ
prpB	2-methylisocitrate lyase	SMc00768
prpC	2-methylcitrate synthase	SMc02087
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	SMc00497
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 17 2021. The underlying query database was built on Sep 17 2021.