GapMind for Amino acid biosynthesis

 

L-lysine biosynthesis in Dinoroseobacter shibae DFL-12

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 (21 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase Dshi_2061
asd aspartate semi-aldehyde dehydrogenase Dshi_3240
dapA 4-hydroxy-tetrahydrodipicolinate synthase Dshi_0149 Dshi_2446
dapB 4-hydroxy-tetrahydrodipicolinate reductase Dshi_3040
dapD tetrahydrodipicolinate succinylase Dshi_0006
dapC N-succinyldiaminopimelate aminotransferase Dshi_3317 Dshi_0798
dapE succinyl-diaminopimelate desuccinylase Dshi_0012 Dshi_3020
dapF diaminopimelate epimerase Dshi_3228
lysA diaminopimelate decarboxylase Dshi_3059 Dshi_1375
Alternative steps:
dapH tetrahydrodipicolinate acetyltransferase Dshi_0006 Dshi_2161
dapL N-acetyl-diaminopimelate deacetylase Dshi_1161 Dshi_1288
DAPtransferase L,L-diaminopimelate aminotransferase Dshi_0762 Dshi_0060
dapX acetyl-diaminopimelate aminotransferase Dshi_0762 Dshi_1168
ddh meso-diaminopimelate D-dehydrogenase
hcs homocitrate synthase Dshi_0596 Dshi_1696
hicdh homo-isocitrate dehydrogenase Dshi_0775 Dshi_3393
lysJ [LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase Dshi_0798 Dshi_1366
lysK [LysW]-lysine hydrolase / [LysW]-ornithine hydrolase
lysN 2-aminoadipate:2-oxoglutarate aminotransferase Dshi_0762 Dshi_0798
lysT homoaconitase large subunit Dshi_0085 Dshi_0695
lysU homoaconitase small subunit Dshi_0083 Dshi_0696
lysW 2-aminoadipate/glutamate carrier protein
lysX 2-aminoadipate-LysW ligase
lysY [LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase Dshi_1759
lysZ [LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase Dshi_0324

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