GapMind for Amino acid biosynthesis

 

Definition of L-tyrosine biosynthesis

As rules and steps, or see full text

Rules

Overview: Tyrosine biosynthesis in GapMind is based on MetaCyc pathways L-tyrosine biosynthesis I via 3-(4-hydroxyphenyl)pyruvate (link), pathway II via L-arogenate (link), pathway III via L-arogenate (link), or pathway IV via phenylalanine (link). Pathway II and III are identical except that different cofactors are used by L-arogenate dehydrogenase; these are not distinguished in GapMind. Pathways I and II/III both involve prephenate; in pathway I, prephenate is oxidized to hydroxyphenylpyruvate before being aminated, while in II/III, prephenate is aminated to arogenate before being oxidized to tyrosine. These alternatives are difficult to distinguish by sequence analysis. MetaCyc describes pathway IV as occuring in metazoa, but it also seems to be the main path to tyrosine in some aerobic bacteria (PMC7311316).

Steps

cmutase: chorismate mutase

ptransferase: prephenate aminotransferase

pre-dehydr: prephenate dehydrogenase

tyrB: tyrosine aminotransferase

aro-dehydr: arogenate dehydrogenase

PAH: phenylalanine hydroxylase

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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