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 or O-succinylserine 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 (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