GapMind for Amino acid biosynthesis

 

Definition of L-cysteine biosynthesis

As rules and steps, or see full text

Rules

Overview: Cysteine biosynthesis in GapMind is based on MetaCyc pathways L-cysteine biosynthesis I from serine and sulfide (link), II (tRNA-dependent) (link), III from serine and homocysteine (link), V (protein-bound thiocarboxylates) (link), VIII via serine kinase (link), or IX via phosphoserine (link). There is no pathway IV. Pathway VI (from serine + methionine) is not included because it is not found in prototrophic bacteria. (It is found in H. pylori, which lacks biosynthesis of homocysteine or methionine; also, it is a supserset of the reactions in pathway III, from serine and homocysteine.) Pathway VII is not included because it requires sulfocysteine, an uncommon precursor. GapMind also describes cysteine biosynthesis with O-succinylserine as an intermediate (PMID:28581482), instead of O-acetylserine (as in pathway I).

Steps

cysE: serine acetyltransferase

cysK: O-acetylserine sulfhydrylase

SST: serine O-succinyltransferase

CBS: cystathionine beta-synthase

CGL: cystathionine gamma-lyase

sepS: O-phosphoseryl-tRNA ligase

pscS: Sep-tRNA:Cys-tRNA synthase

Mt_cysM: CysO-thiocarboxylate-dependent cysteine synthase

mec: [CysO sulfur-carrier protein]-S-L-cysteine hydrolase

moeZ: [sulfur carrier protein CysO]--sulfur ligase

cysO: sulfur carrier protein CysO

PSSH: O-phosphoserine sulfhydrylase

serK: serine kinase (ADP-dependent)

serA: 3-phosphoglycerate dehydrogenase

serC: 3-phosphoserine aminotransferase

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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