L-valine catabolism in Amycolatopsis halophila YIM 93223

GapMind for catabolism of small carbon sources

L-valine catabolism in Amycolatopsis halophila YIM 93223

Best path

natA, natB, natC, natD, natE, bkdA, bkdB, bkdC, lpd, acdH, ech, bch, mmsB, mmsA, pccA, pccB, epi, mcm-large, mcm-small

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 (33 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
natA	L-valine ABC transporter, ATPase component 1 (NatA)	AMYHA_RS16245	AMYHA_RS07110
natB	L-valine ABC transporter, substrate-binding component NatB	AMYHA_RS16235
natC	L-valine ABC transporter, permease component 1 (NatC)
natD	L-valine ABC transporter, permease component 2 (NatD)	AMYHA_RS16255	AMYHA_RS10530
natE	L-valine ABC transporter, ATPase component 2 (NatE)	AMYHA_RS16240	AMYHA_RS20895
bkdA	branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit	AMYHA_RS03550	AMYHA_RS07890
bkdB	branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit	AMYHA_RS07885	AMYHA_RS03555
bkdC	branched-chain alpha-ketoacid dehydrogenase, E2 component	AMYHA_RS07880	AMYHA_RS03560
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	AMYHA_RS04850	AMYHA_RS18755
acdH	isobutyryl-CoA dehydrogenase	AMYHA_RS09585	AMYHA_RS19255
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	AMYHA_RS20710	AMYHA_RS24905
bch	3-hydroxyisobutyryl-CoA hydrolase
mmsB	3-hydroxyisobutyrate dehydrogenase	AMYHA_RS19775	AMYHA_RS17060
mmsA	methylmalonate-semialdehyde dehydrogenase	AMYHA_RS14120	AMYHA_RS20335
pccA	propionyl-CoA carboxylase, alpha subunit	AMYHA_RS25215	AMYHA_RS19995
pccB	propionyl-CoA carboxylase, beta subunit	AMYHA_RS25160	AMYHA_RS19150
epi	methylmalonyl-CoA epimerase	AMYHA_RS10325
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	AMYHA_RS25265	AMYHA_RS22150
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	AMYHA_RS25265	AMYHA_RS22150
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	AMYHA_RS15065
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	AMYHA_RS15065
Bap2	L-valine permease Bap2
bcaP	L-valine uptake transporter BcaP/CitA
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB
dddA	3-hydroxypropionate dehydrogenase	AMYHA_RS20340	AMYHA_RS26645
hpcD	3-hydroxypropionyl-CoA dehydratase	AMYHA_RS20710	AMYHA_RS06590
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	AMYHA_RS14120	AMYHA_RS20335
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	AMYHA_RS20895	AMYHA_RS07105
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	AMYHA_RS05545	AMYHA_RS20900
livH	L-valine ABC transporter, permease component 1 (LivH/BraD)	AMYHA_RS04370	AMYHA_RS16255
livJ	L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)
livM	L-valine ABC transporter, permease component 2 (LivM/BraE)	AMYHA_RS10525	AMYHA_RS07095
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	AMYHA_RS25265	AMYHA_RS16400
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	AMYHA_RS01155
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	AMYHA_RS19995	AMYHA_RS25215
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	AMYHA_RS24060	AMYHA_RS09585
phtJ	L-valine uptake permease PhtJ
prpB	2-methylisocitrate lyase	AMYHA_RS20455	AMYHA_RS10340
prpC	2-methylcitrate synthase	AMYHA_RS06260	AMYHA_RS06280
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	AMYHA_RS01150
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.

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Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
SQLite3 databases

Related tools

About GapMind

Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.

A candidate for a step is "high confidence" if either:

ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.

where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").

Otherwise, a candidate is "medium confidence" if either:

ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
HMMer finds a hit (regardless of coverage or other bits).

Other blast hits with at least 50% coverage are "low confidence."

Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:

our ignorance of proteins' functions,
omissions in the gene models,
frame-shift errors in the genome sequence, or
the organism lacks the pathway.

GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).

For more information, see:

the paper from 2019 on GapMind for amino acid biosynthesis
the 2024 update on GapMind for amino acid biosynthesis
the paper from 2022 on GapMind for carbon sources
the source code
instructions for running GapMind on your computer

If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know

by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory

GapMind for catabolism of small carbon sources