GapMind for Amino acid biosynthesis


L-isoleucine biosynthesis in Sphingomonas koreensis DSMZ 15582

Best path

ilvA, ilvI, ilvH, ilvC, ilvD, ilvE

Also see fitness data for the top candidates


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 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 (12 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
ilvA threonine deaminase Ga0059261_3694 Ga0059261_3754
ilvI acetohydroxybutanoate synthase regulatory subunit Ga0059261_0067
ilvH acetohydroxybutanoate synthase catalytic subunit Ga0059261_0068 Ga0059261_0285
ilvC 2-hydroxy-3-ketol-acid reductoisomerase Ga0059261_0066
ilvD (R)-2,3-dihydroxy-3-methylpentanoate dehydratase Ga0059261_4216 Ga0059261_2649
ilvE isoleucine transaminase Ga0059261_3811 Ga0059261_1688
Alternative steps:
cimA (R)-citramalate synthase
leuB 3-methylmalate dehydrogenase Ga0059261_3190
leuC citramalate isomerase large subunit Ga0059261_4223
leuD citramalate isomerase small subunit Ga0059261_4225 Ga0059261_3296
ofoa 2-oxobutanoate:ferredoxin oxidoreductase, alpha subunit Ga0059261_0325
ofob 2-oxobutanoate:ferredoxin oxidoreductase, beta subunit Ga0059261_0324
prpE propionyl-CoA synthetase Ga0059261_1313 Ga0059261_0337

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:

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