GapMind for Amino acid biosynthesis

 

Definition of L-proline biosynthesis

As rules and steps, or see full text

Rules

Overview: Proline biosynthesis in GapMind is based on MetaCyc pathways L-proline biosynthesis I from L-glutamate (link) and III via L-ornithine aminotransferase (link). GapMind also describes proline synthesis via ornithine cyclodeaminase (PMID:11489875). Pathway II from arginine (link) should perhaps be included, but is not; it is reported in nitrogen-fixing cyanobacteria and the bacteria it was reported in also have pathway I. Pathway IV is not included because it is not reported in prokaryotes (link). Also, pathway III is described in MetaCyc as occuring only in plants, but it also is reported in the archaeon Thermococcus kodakarensis (PMC5846162).

Steps

lysW: 2-aminoadipate/glutamate carrier protein

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

argA: N-acylglutamate synthase

argB: N-acylglutamate kinase

argC: N-acylglutamylphosphate reductase

argD: N-acetylornithine aminotransferase

argE: N-acetylornithine deacetylase

argJ: ornithine acetyltransferase

argX: glutamate--LysW ligase

proB: glutamate 5-kinase

proA: gamma-glutamylphosphate reductase

proC: pyrroline-5-carboxylate reductase

OAT: L-ornithine 5-aminotransferase

cyclodeaminase: ornithine cyclodeaminase

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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, 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