GapMind for Amino acid biosynthesis

 

L-lysine biosynthesis in Shewanella sp. ANA-3

Best path

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

Also see fitness data for the top candidates

Rules

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 (20 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase Shewana3_1139 Shewana3_3613
asd aspartate semi-aldehyde dehydrogenase Shewana3_1477
dapA 4-hydroxy-tetrahydrodipicolinate synthase Shewana3_1656
dapB 4-hydroxy-tetrahydrodipicolinate reductase Shewana3_0966
dapD tetrahydrodipicolinate succinylase Shewana3_2818
dapC N-succinyldiaminopimelate aminotransferase Shewana3_1973 Shewana3_0610
dapE succinyl-diaminopimelate desuccinylase Shewana3_1912
dapF diaminopimelate epimerase Shewana3_0391
lysA diaminopimelate decarboxylase Shewana3_0390
Alternative steps:
dapH tetrahydrodipicolinate acetyltransferase Shewana3_0322 Shewana3_2818
dapL N-acetyl-diaminopimelate deacetylase Shewana3_3941
DAPtransferase L,L-diaminopimelate aminotransferase Shewana3_2903
dapX acetyl-diaminopimelate aminotransferase
ddh meso-diaminopimelate D-dehydrogenase
hcs homocitrate synthase Shewana3_3761
hicdh homo-isocitrate dehydrogenase Shewana3_2890 Shewana3_3760
lysJ [LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase Shewana3_0610 Shewana3_3091
lysK [LysW]-lysine hydrolase / [LysW]-ornithine hydrolase
lysN 2-aminoadipate:2-oxoglutarate aminotransferase Shewana3_3091 Shewana3_0610
lysT homoaconitase large subunit Shewana3_3759
lysU homoaconitase small subunit Shewana3_3758 Shewana3_3827
lysW 2-aminoadipate/glutamate carrier protein
lysX 2-aminoadipate-LysW ligase Shewana3_2405
lysY [LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase Shewana3_3905
lysZ [LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase

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