GapMind for Amino acid biosynthesis


L-lysine biosynthesis in Klebsiella michiganensis M5al

Best path

asp-kinase, asd, dapA, dapB, dapD, dapC, dapE, dapF, lysA

Also see fitness data for the top candidates


Overview: Lysine biosynthesis in GapMind is based on MetaCyc pathways L-lysine biosynthesis I via diaminopimelate (DAP) and succinylated intermediates (link), II with DAP and acetylated intermediates (link), III with DAP and no blocking group (link), V via 2-aminoadipate and LysW carrier protein (link), and VI with DAP aminotransferase (link). Most of these pathways involve tetrahydrodipicolinate and meso-diaminopimelate, with variations in how the amino group is introduced. Pathway V instead involves L-2-aminoadipate and LysW-attached intermediates. Lysine biosynthesis IV (link), via 2-aminoadipate and saccharopine, is only reported to occur in eukaryotes and is not described here.

25 steps (21 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase BWI76_RS04245 BWI76_RS00790
asd aspartate semi-aldehyde dehydrogenase BWI76_RS26220 BWI76_RS12880
dapA 4-hydroxy-tetrahydrodipicolinate synthase BWI76_RS20905 BWI76_RS05685
dapB 4-hydroxy-tetrahydrodipicolinate reductase BWI76_RS04460
dapD tetrahydrodipicolinate succinylase BWI76_RS05195
dapC N-succinyldiaminopimelate aminotransferase BWI76_RS26000 BWI76_RS09755
dapE succinyl-diaminopimelate desuccinylase BWI76_RS20870 BWI76_RS14620
dapF diaminopimelate epimerase BWI76_RS01200
lysA diaminopimelate decarboxylase BWI76_RS23360
Alternative steps:
dapH tetrahydrodipicolinate acetyltransferase BWI76_RS05195 BWI76_RS00615
dapL N-acetyl-diaminopimelate deacetylase BWI76_RS16785 BWI76_RS13530
DAPtransferase L,L-diaminopimelate aminotransferase BWI76_RS20495
dapX acetyl-diaminopimelate aminotransferase BWI76_RS10245 BWI76_RS20495
ddh meso-diaminopimelate D-dehydrogenase
hcs homocitrate synthase BWI76_RS18860 BWI76_RS04680
hicdh homo-isocitrate dehydrogenase BWI76_RS11330 BWI76_RS10680
lysJ [LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase BWI76_RS11670 BWI76_RS24630
lysK [LysW]-lysine hydrolase / [LysW]-ornithine hydrolase
lysN 2-aminoadipate:2-oxoglutarate aminotransferase BWI76_RS10245 BWI76_RS26375
lysT homoaconitase large subunit BWI76_RS04670
lysU homoaconitase small subunit BWI76_RS04665
lysW 2-aminoadipate/glutamate carrier protein
lysX 2-aminoadipate-LysW ligase
lysY [LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase BWI76_RS00845
lysZ [LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase BWI76_RS00850

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 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