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

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

lysJ: [LysW]-2-aminoadipate semialdehyde transaminase

lysK: [LysW]-lysine 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 (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:

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