GapMind for Amino acid biosynthesis

 

Definition of L-valine biosynthesis

As text, or see rules and steps

# Valine biosynthesis in GapMind is based on MetaCyc pathway L-valine biosynthesis
# (metacyc:VALSYN-PWY).

# ilvIH (or ilvGM) is a two-subunit enzyme that forms acetolactate or acetohydroxybutanoate.
# BRENDA often annotates both subunits the same, so it is unclear which is which.
# CH_124129 and CH_123884 are probably correct but have limited data and vaguer annotations.
#
ilvH	acetohydroxybutanoate synthase catalytic subunit	hmm:TIGR00118	term:acetohydroxy-acid synthase%large	term:acetohydroxy acid synthase%large	term:acetohydroxybutanoate synthase, catalytic subunit	term:acetohydroxybutanoate synthase, catalytic subunit	term:acetohydroxyacid synthase subunit B	ignore_other:EC 2.2.1.6	ignore:CharProtDB::CH_124219	ignore:CharProtDB::CH_123884

# The isolated catalytic subunit has some activity so it's not clear if the regulatory
# subunit should be required.
ilvI	acetohydroxybutanoate synthase regulatory subunit 	hmm:TIGR00119	term:acetohydroxy-acid synthase%small	term:acetohydroxybutanoate synthase, regulatory subunit	term:small subunit of acetolactate synthase	ignore_other:EC 2.2.1.6

# The various EC numbers vary in their preference for NAD(P)H.
ilvC	ketol-acid reductoisomerase	EC:1.1.1.86	EC:1.1.1.382	EC:1.1.1.383

# The ignored enzyme is involved in salinosporamide A biosynthesis but does a very similar reaction
# and is >50% identical to N515DRAFT_0569, which is confirmed by fitness data to be biosynthetic.
ilvD	(R)-2,3-dihydroxy-3-methylbutanoate dehydratase	EC:4.2.1.9	ignore:metacyc::MONOMER-15882

ilvE	valine transaminase	EC:2.6.1.42

all: ilvH ilvI ilvC ilvD ilvE

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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:

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:

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:

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 paper from 2022 on GapMind for carbon sources, or view the source code, or see changes to Amino acid biosynthesis since the publication.

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