GapMind for Amino acid biosynthesis

 

L-isoleucine biosynthesis in Shewanella sp. ANA-3

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. Pathway V, from 2-methylbutanoate (link), is not included.

13 steps (11 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
ilvA threonine deaminase Shewana3_0359
ilvI acetohydroxybutanoate synthase regulatory subunit Shewana3_2270 Shewana3_0357
ilvH acetohydroxybutanoate synthase catalytic subunit Shewana3_2269 Shewana3_0356
ilvC 2-hydroxy-3-ketol-acid reductoisomerase Shewana3_0355
ilvD (R)-2,3-dihydroxy-3-methylpentanoate dehydratase Shewana3_0358 Shewana3_2070
ilvE isoleucine transaminase Shewana3_3830 Shewana3_2121
Alternative steps:
cimA (R)-citramalate synthase Shewana3_3761
leuB 3-methylmalate dehydrogenase Shewana3_3760 Shewana3_2890
leuC citramalate isomerase large subunit Shewana3_3759 Shewana3_3827
leuD citramalate isomerase small subunit Shewana3_3758 Shewana3_3827
ofoa 2-oxobutanoate:ferredoxin oxidoreductase, alpha subunit
ofob 2-oxobutanoate:ferredoxin oxidoreductase, beta subunit
prpE propionyl-CoA synthetase Shewana3_1675 Shewana3_2523

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.

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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 preprint 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