GapMind for Amino acid biosynthesis


L-isoleucine biosynthesis in Tistlia consotensis USBA 355

Best path

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


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. 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 (13 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
cimA (R)-citramalate synthase B9O00_RS31655 B9O00_RS01945
leuC 3-isopropylmalate dehydratase / citramalate isomerase, large subunit B9O00_RS08285
leuD 3-isopropylmalate dehydaratase / citramalate isomerase, small subunit B9O00_RS08290 B9O00_RS08500
leuB 3-methylmalate dehydrogenase / 3-isopropylmalate dehydrogenase B9O00_RS08305 B9O00_RS23510
ilvI acetolactate/acetohydroxybutanoate synthase catalytic subunit B9O00_RS01975 B9O00_RS27935
ilvH acetolactate/acetohydroxybutanoate synthase regulatory subunit B9O00_RS01970
ilvC 2-hydroxy-3-ketol-acid reductoisomerase B9O00_RS01965
ilvD dihydroxy-acid dehydratase B9O00_RS09740 B9O00_RS04150
ilvE isoleucine transaminase B9O00_RS22765 B9O00_RS29405
Alternative steps:
ilvA threonine deaminase B9O00_RS17765 B9O00_RS10660
ofoa 2-oxobutanoate:ferredoxin oxidoreductase, alpha subunit B9O00_RS10290
ofob 2-oxobutanoate:ferredoxin oxidoreductase, beta subunit B9O00_RS10285
prpE propionyl-CoA synthetase B9O00_RS14455 B9O00_RS28395

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