GapMind for Amino acid biosynthesis

 

L-lysine biosynthesis in Pedobacter sp. GW460-11-11-14-LB5

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 Class of gap
asp-kinase aspartate kinase CA265_RS23475 CA265_RS09655  
asd aspartate semi-aldehyde dehydrogenase CA265_RS15395  
dapA 4-hydroxy-tetrahydrodipicolinate synthase CA265_RS02050 CA265_RS08390  
dapB 4-hydroxy-tetrahydrodipicolinate reductase CA265_RS15670  
dapD tetrahydrodipicolinate succinylase CA265_RS02995  
dapC N-succinyldiaminopimelate aminotransferase CA265_RS09005 CA265_RS03895  
dapE? succinyl-diaminopimelate desuccinylase novel
dapF diaminopimelate epimerase CA265_RS23025  
lysA diaminopimelate decarboxylase CA265_RS09650  
Alternative steps:
dapH tetrahydrodipicolinate acetyltransferase CA265_RS02995 CA265_RS05165  
dapL N-acetyl-diaminopimelate deacetylase CA265_RS17965 CA265_RS23900  
DAPtransferase L,L-diaminopimelate aminotransferase CA265_RS15090  
dapX acetyl-diaminopimelate aminotransferase CA265_RS07515  
ddh meso-diaminopimelate D-dehydrogenase  
hcs homocitrate synthase CA265_RS15855  
hicdh homo-isocitrate dehydrogenase CA265_RS15850  
lysJ [LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase CA265_RS18530 CA265_RS15205  
lysK [LysW]-lysine hydrolase / [LysW]-ornithine hydrolase  
lysN 2-aminoadipate:2-oxoglutarate aminotransferase CA265_RS07515 CA265_RS18530  
lysT homoaconitase large subunit CA265_RS16405 CA265_RS15830  
lysU homoaconitase small subunit CA265_RS15840 CA265_RS16405  
lysW 2-aminoadipate/glutamate carrier protein  
lysX 2-aminoadipate-LysW ligase  
lysY [LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase CA265_RS18540  
lysZ [LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase CA265_RS18510  

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 Mar 30 2021. The underlying query database was built on Mar 30 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 against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer. 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. 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, 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