L-valine catabolism in Rhodospirillum rubrum ATCC 11170

Best path

livF, livG, livJ, livH, livM, ofo, 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 (39 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	Rru_A1748	Rru_A3725
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	Rru_A1749	Rru_A3724
livJ	L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)	Rru_A1746	Rru_A2171
livH	L-valine ABC transporter, permease component 1 (LivH/BraD)	Rru_A1751	Rru_A3726
livM	L-valine ABC transporter, permease component 2 (LivM/BraE)	Rru_A1750	Rru_A3727
ofo	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused	Rru_A2185
acdH	isobutyryl-CoA dehydrogenase	Rru_A1835	Rru_A1948
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	Rru_A3801	Rru_A2156
bch	3-hydroxyisobutyryl-CoA hydrolase	Rru_A1834	Rru_A3801
mmsB	3-hydroxyisobutyrate dehydrogenase	Rru_A1833
mmsA	methylmalonate-semialdehyde dehydrogenase	Rru_A1542	Rru_A2071
prpC	2-methylcitrate synthase	Rru_A2319	Rru_A1600
prpD	2-methylcitrate dehydratase	Rru_A2318
acn	(2R,3S)-2-methylcitrate dehydratase	Rru_A3511
prpB	2-methylisocitrate lyase	Rru_A2320
Alternative steps:
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	Rru_A3511
Bap2	L-valine permease Bap2
bcaP	L-valine uptake transporter BcaP/CitA
bkdA	branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit	Rru_A1881
bkdB	branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit	Rru_A1880
bkdC	branched-chain alpha-ketoacid dehydrogenase, E2 component	Rru_A1214	Rru_A1879
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB
dddA	3-hydroxypropionate dehydrogenase
epi	methylmalonyl-CoA epimerase	Rru_A1572
hpcD	3-hydroxypropionyl-CoA dehydratase	Rru_A3801	Rru_A2506
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	Rru_A2071	Rru_A1542
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	Rru_A1878	Rru_A1215
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	Rru_A2479	Rru_A3062
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	Rru_A3062	Rru_A2479
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	Rru_A2479	Rru_A2480
natA	L-valine ABC transporter, ATPase component 1 (NatA)	Rru_A3414	Rru_A3724
natB	L-valine ABC transporter, substrate-binding component NatB	Rru_A1746
natC	L-valine ABC transporter, permease component 1 (NatC)	Rru_A3415
natD	L-valine ABC transporter, permease component 2 (NatD)	Rru_A3416	Rru_A3306
natE	L-valine ABC transporter, ATPase component 2 (NatE)	Rru_A3413	Rru_A1748
ofoA	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit OfoA	Rru_A2721
ofoB	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit OfoB	Rru_A2722
pccA	propionyl-CoA carboxylase, alpha subunit	Rru_A0052	Rru_A1941
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	Rru_A0052	Rru_A2435
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	Rru_A1941
pccB	propionyl-CoA carboxylase, beta subunit	Rru_A0053	Rru_A1943
pco	propanyl-CoA oxidase	Rru_A2005
phtJ	L-valine uptake permease PhtJ
prpF	methylaconitate isomerase
vorA	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit VorA
vorB	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit VorB	Rru_A2721
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.