GapMind for Amino acid biosynthesis

 

Definition of L-lysine biosynthesis

As rules and steps, or see full text

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.

Steps

asp-kinase: aspartate kinase

asd: aspartate semi-aldehyde dehydrogenase

dapA: 4-hydroxy-tetrahydrodipicolinate synthase

dapB: 4-hydroxy-tetrahydrodipicolinate reductase

dapD: tetrahydrodipicolinate succinylase

dapC: N-succinyldiaminopimelate aminotransferase

dapE: succinyl-diaminopimelate desuccinylase

dapF: diaminopimelate epimerase

lysA: diaminopimelate decarboxylase

dapH: tetrahydrodipicolinate acetyltransferase

dapX: acetyl-diaminopimelate aminotransferase

dapL: N-acetyl-diaminopimelate deacetylase

ddh: meso-diaminopimelate D-dehydrogenase

DAPtransferase: L,L-diaminopimelate aminotransferase

hcs: homocitrate synthase

lysT: homoaconitase large subunit

lysU: homoaconitase small subunit

hicdh: homo-isocitrate dehydrogenase

lysN: 2-aminoadipate:2-oxoglutarate aminotransferase

lysW: 2-aminoadipate/glutamate carrier protein

lysX: 2-aminoadipate-LysW ligase

lysZ: [LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase

lysY: [LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase

lysJ: [LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase

lysK: [LysW]-lysine hydrolase / [LysW]-ornithine hydrolase

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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