GapMind for Amino acid biosynthesis

 

L-isoleucine biosynthesis in Cupriavidus basilensis FW507-4G11

Best path

ilvA, ilvI, ilvH, ilvC, ilvD, ilvE

Also see fitness data for the top candidates

Rules

Overview: Isoleucine biosynthesis in GapMind is based on MetaCyc pathways L-isoleucine biosynthesis I (from threonine) (link), II via citramalate (link), or IV from propanoate (link). These pathways share a common intermediate, 2-oxobutanoate, but vary in how the 2-oxobutanoate is formed. Pathway IV is included because propanoate is a common fermentative end product and need not be a nutrient requirement, but it is not always clear if it could be the main pathway to isoleucine. Pathway III (link), via glutamate mutase, is not included because the first step (glutamate mutase, EC 5.4.99.1) has not been linked to sequence and because no organism has been demonstrated to rely on this pathway to form oxobutanoate. MetaCyc L-isoleucine biosynthesis V describes biosynthesis from 2-methylbutanoate, which is a fermentation end product in the rumen; this is an an unusual precursor so we did not include it.

13 steps (11 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
ilvA threonine deaminase RR42_RS02315 RR42_RS33880
ilvI acetolactate/acetohydroxybutanoate synthase catalytic subunit RR42_RS05435 RR42_RS31370
ilvH acetolactate/acetohydroxybutanoate synthase regulatory subunit RR42_RS05440
ilvC 2-hydroxy-3-ketol-acid reductoisomerase RR42_RS05445
ilvD dihydroxy-acid dehydratase RR42_RS16210 RR42_RS33950
ilvE isoleucine transaminase RR42_RS25890 RR42_RS14595
Alternative steps:
cimA (R)-citramalate synthase RR42_RS05465
leuB 3-methylmalate dehydrogenase / 3-isopropylmalate dehydrogenase RR42_RS14385 RR42_RS33755
leuC 3-isopropylmalate dehydratase / citramalate isomerase, large subunit RR42_RS14400 RR42_RS24175
leuD 3-isopropylmalate dehydaratase / citramalate isomerase, small subunit RR42_RS14390 RR42_RS24180
ofoa 2-oxobutanoate:ferredoxin oxidoreductase, alpha subunit
ofob 2-oxobutanoate:ferredoxin oxidoreductase, beta subunit
prpE propionyl-CoA synthetase RR42_RS13880 RR42_RS13560

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 Apr 09 2024. The underlying query database was built on Apr 09 2024.

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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:

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