L-leucine biosynthesis in Cupriavidus basilensis 4G11

GapMind for Amino acid biosynthesis

L-leucine biosynthesis in Cupriavidus basilensis 4G11

Best path

ilvH, ilvI, ilvC, ilvD, leuA, leuC, leuD, leuB, ilvE

Also see fitness data for the top candidates

Rules

Overview: Leucine biosynthesis in GapMind is based on MetaCyc pathway L-leucine biosynthesis (link). This begins with the initial steps of valine biosynthesis (see link), up to 3-methyloxobutanoate.

all: ilvH, ilvI, ilvC, ilvD, leuA, leuC, leuD, leuB and ilvE

9 steps (9 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
ilvH	acetohydroxybutanoate synthase catalytic subunit	RR42_RS05435	RR42_RS36655
ilvI	acetohydroxybutanoate synthase regulatory subunit	RR42_RS05440
ilvC	ketol-acid reductoisomerase	RR42_RS05445
ilvD	(R)-2,3-dihydroxy-3-methylbutanoate dehydratase	RR42_RS16210	RR42_RS33950
leuA	2-isopropylmalate synthase	RR42_RS21205	RR42_RS05465
leuC	3-isopropylmalate dehydratase, large subunit	RR42_RS14400	RR42_RS24175
leuD	3-isopropylmalate dehydaratase, small subunit	RR42_RS24180	RR42_RS14390
leuB	3-isopropylmalate dehydrogenase	RR42_RS02600	RR42_RS14385
ilvE	leucine transaminase	RR42_RS25890	RR42_RS14595

Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway

This GapMind analysis is from Aug 03 2021. The underlying query database was built on Aug 03 2021.

Downloads

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 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

GapMind for Amino acid biosynthesis