GapMind for Amino acid biosynthesis

 

Definition of L-arginine biosynthesis

As rules and steps, or see full text

Rules

Overview: Arginine biosynthesis in GapMind is based on MetaCyc pathways L-arginine biosynthesis I via L-acetyl-ornithine (link), II (acetyl cycle) (link), III via N-acetyl-L-citrulline (link), or IV via LysW-ornithine (link). GapMind also includes L-arginine biosynthesis with succinylated intermediates, as in Bacteroidetes (PMC5764234). These pathways all involve the activation of glutamate (by aceylation, succinylation, or attachment of LysW), followed by phosphorylation, reduction and transamination, to activated ornithine. In most pathways, this intermediate is cleaved to ornithine before transcarbamoylation, but in the N-acetylcitrulline or succinylated pathways, transcarbamoylation occurs before hydrolysis. In the final two steps, citrulline is converted to arginine by ArgG and ArgH.

Steps

argA: N-acylglutamate synthase

argB: N-acylglutamate kinase

argC: N-acylglutamylphosphate reductase

argD: N-acetylornithine aminotransferase

argE: N-acetylornithine deacetylase

carA: carbamoyl phosphate synthase subunit alpha

carB: carbamoyl phosphate synthase subunit beta

argI: ornithine carbamoyltransferase

argG: arginosuccinate synthetase

argH: arginosuccinate lyase

argD'B: N-succinylornithine aminotransferase

argF'B: N-succinylornithine carbamoyltransferase

argE'B: N-succinylcitrulline desuccinylase

argJ: ornithine acetyltransferase

argF': acetylornithine transcarbamoylase

argX: glutamate--LysW ligase

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

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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