Definition of L-valine catabolism

GapMind for catabolism of small carbon sources

Definition of L-valine catabolism

# Valine degradation in GapMind is based on
# MetaCyc pathway L-valine degradation I (metacyc:VALDEG-PWY).
# The other pathways do not produce any fixed carbon and are not included.


# ABC transporters with 5 components: E. coli livFGHMJ and related systems
# (but the alternate substrate-binding protein livK does not transport valine).
# Related systems include
# livJFGHM from Streptococcus pneumoniae,
# braCDEFG from Pseudomonas aeruginosa (braC is the SBP),
# and braCDEFG or braC3/braDEFG from R. leguminosarum.
#    In R. leguminosarum, the proximal braC (Q9L3M3) transports leucine (PMC135202), and likely valine as well.
#    braC3 (RL3540; Q1MDE9) is a secondary SBP that transports leucine/isoleucine/valine/alanine (PMID:19597156).
#    LivH/BraD = RL3750/Q1MCU0; LivM/BraE = RL3749/Q1MCU1;
#    LivG/BraF = RL3748/Q1MCU2; LivF/BraG = RL3747/Q1MCU3.
# (The related liv system from Acidovorax, Ac3H11_1692:1695 and Ac3H11_2396,
#  has not been shown to transport valine.)
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	curated:CharProtDB::CH_003736	curated:TCDB::P21630	curated:TCDB::Q8DQH7	uniprot:Q1MCU3

livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	curated:TCDB::P0A9S7	curated:TCDB::P21629	curated:TCDB::Q8DQH8	uniprot:Q1MCU2

livJ	L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)	curated:SwissProt::P21175	curated:TCDB::P0AD96	curated:TCDB::Q8DQI1	uniprot:Q1MDE9	curated:TCDB::Q9L3M3

livH	L-valine ABC transporter, permease component 1 (LivH/BraD)	curated:TCDB::P21627	curated:TCDB::Q8DQI0	curated:ecocyc::LIVH-MONOMER	uniprot:Q1MCU0

# LivM from Streptococcus pneumoniae lacks an N-terminal domain of unknown
# function (DUF3382) that is found in E.coli and P. aeruginosa
livM	L-valine ABC transporter, permease component 2 (LivM/BraE)	curated:SwissProt::P22729	curated:TCDB::P21628	curated:TCDB::Q8DQH9	uniprot:Q1MCU1

# Transporters were identified using
# query: transporter:valine:L-valine:val
valine-transport: livF livG livJ livH livM


# Synechocystis sp. NatABCDE TC 3.A.1.4.2) and a similar system from
# Anabaena (also known as N-I; TC 3.A.1.4.6) are reported to transport
# many amino acids. There isn't any data for valine transport in
# Synechocystis, but N-I from Anabaena is thought to contribute to the
# reuptake of valine that leaks from the cell (PMC4500139).
natA	L-valine ABC transporter, ATPase component 1 (NatA)	ignore:TCDB::Q55164	curated:TCDB::Q7A2H0
natB	L-valine ABC transporter, substrate-binding component NatB	ignore:TCDB::Q55387	curated:TCDB::Q8YVY4
natC	L-valine ABC transporter, permease component 1 (NatC)	ignore:TCDB::P74455	curated:TCDB::Q8YY08
natD	L-valine ABC transporter, permease component 2 (NatD)	ignore:TCDB::P74318	curated:TCDB::Q8YXD0
natE	L-valine ABC transporter, ATPase component 2 (NatE)	ignore:TCDB::P73650	curated:TCDB::Q8YT15
valine-transport: natA natB natC natD natE

Bap2	L-valine permease Bap2	curated:CharProtDB::CH_091448	curated:CharProtDB::CH_091631	curated:SwissProt::P38084	curated:SwissProt::P41815	curated:TCDB::Q2VQZ4
valine-transport: Bap2

# E. coli BrnQ is reported to use Na+, while P. aeruginosa BraZ is reported to use H+
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB	curated:TCDB::P0AD99	curated:TCDB::P25185	curated:TCDB::P19072
valine-transport: brnQ

phtJ	L-valine uptake permease PhtJ	curated:TCDB::Q5ZUB4
valine-transport: phtJ

bcaP	L-valine uptake transporter BcaP/CitA	curated:TCDB::S6EX81
valine-transport: bcaP

# Non-specific large neutral amino acid tranpsorters from mammals were ignored
# Amino acid efflux pumps were ignored


# propionyl-CoA is an intermediate in valine degradation
import propionate.steps:propionyl-CoA-degradation

# 3-methyl-2-oxobutanoate dehydrogenase is one of the activities of
# branched-chain alpha-ketoacid dehydrogenases, which pass electrons
# to NAD (EC:1.2.1.25) or ferredoxin (EC:1.2.7.7)
import leucine.steps:BKD

# EC:1.3.8.5 includes isobutyryl-CoA dehydrogenases and sometimes
# (2S)-2-methylbutanoyl-CoA dehydrogenases (involved in isoleucine
# degradation, usually given EC:1.3.8.5 as well) or
# 3-methylbutanoyl-CoA dehydrogenases (involved in leucine
# degradation, usually given EC:1.3.8.4). Some enzymes act on all
# three methylacyl-CoA substrates. Other genes are required
# only for isoleucine degradation and their activity on
# isobutyryl-CoA is uncertain, so they are marked ignore.
# Also add Psest_2440 (GFF2392), given a different EC number,
# and ignore PfGW456L13_2983 (given a different EC but
# involved in isoleucine degradation) and
# PP_2216 (MONOMER-17424), also involved in isoleucine
# degradation.
acdH	isobutyryl-CoA dehydrogenase	EC:1.3.8.5	ignore:reanno::MR1:200844	ignore:reanno::WCS417:GFF2715	ignore:reanno::acidovorax_3H11:Ac3H11_2996	ignore:reanno::psRCH2:GFF2397	ignore:reanno::pseudo1_N1B4:Pf1N1B4_4787	ignore:reanno::pseudo5_N2C3_1:AO356_26355	ignore:reanno::pseudo6_N2E2:Pf6N2E2_1146	ignore:reanno::pseudo13_GW456_L13:PfGW456L13_2983	curated:reanno::psRCH2:GFF2392	ignore:metacyc::MONOMER-17424

import phenylacetate.steps:ech # (S)-3-hydroxybutanoyl-CoA hydro-lyase

bch	3-hydroxyisobutyryl-CoA hydrolase	EC:3.1.2.4	ignore:BRENDA::Q9SE41	ignore:metacyc::MONOMER-11695

# D5MU22 is probably mmsB but is misannotated in BRENDA
mmsB	3-hydroxyisobutyrate dehydrogenase	EC:1.1.1.31	ignore:BRENDA::D5MU22

mmsA	methylmalonate-semialdehyde dehydrogenase	EC:1.2.1.27

# 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.
all: valine-transport BKD acdH ech bch mmsB mmsA propionyl-CoA-degradation

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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 preprint on GapMind for carbon sources, or view the source code.

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