L-cysteine biosynthesis in Methanobacterium lacus AL-21

GapMind for Amino acid biosynthesis

L-cysteine biosynthesis in Methanobacterium lacus AL-21

Best path

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).

all:

from-serine
or serA, serC and from-phosphoserine
or from-serine-homocysteine

from-phosphoserine:

sepS and pscS
or cysO, moeZ, Mt_cysM and mec
or PSSH
Comment: Phosphoserine can be converted to cysteine by the tRNA-dependent pathway II (sepS and pscS), the protein-bound thiocarboxylate pathway V with the carrier protein cysO, or by direct sulfhydrylation (PSSH) as in pathway IX.

from-serine-homocysteine: CBS and CGL

Comment: In many organisms, the sulfhydryl group of cysteine is used to form homocysteine and methionine, but this pathway can also run in reverse. GapMind uses a pathway requirement to warn if an organism is modeled as synthesizing methionine and cysteine from each other.

from-serine:

cysE and cysK
or SST and cysK
or serK and PSSH
Comment: Cysteine can be formed from serine via O-acetylserine as in pathway I (cysE and cysK), via O-succinylserine (SST), or via serine kinase (serK) as in pathway IX. For the O-succinylserine pathway, the identity of the O-succinylserine sulfhydrylase is not proven, but it is expected to be similar to cysK.

15 steps (12 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
serA	3-phosphoglycerate dehydrogenase	METBO_RS02145
serC	3-phosphoserine aminotransferase	METBO_RS02880
sepS	O-phosphoseryl-tRNA ligase	METBO_RS00215
pscS	Sep-tRNA:Cys-tRNA synthase	METBO_RS11765
Alternative steps:
CBS	cystathionine beta-synthase	METBO_RS05910
CGL	cystathionine gamma-lyase	METBO_RS06350	METBO_RS06070
cysE	serine acetyltransferase	METBO_RS05905	METBO_RS06075
cysK	O-acetylserine or O-succinylserine sulfhydrylase	METBO_RS05910	METBO_RS06070
cysO	sulfur carrier protein CysO
mec	[CysO sulfur-carrier protein]-S-L-cysteine hydrolase
moeZ	[sulfur carrier protein CysO]--sulfur ligase	METBO_RS06045
Mt_cysM	CysO-thiocarboxylate-dependent cysteine synthase	METBO_RS05910
PSSH	O-phosphoserine sulfhydrylase	METBO_RS05910
serK	serine kinase (ADP-dependent)
SST	serine O-succinyltransferase	METBO_RS06075

Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway

This GapMind analysis is from Apr 10 2024. The underlying query database was built on Apr 09 2024.

Downloads

Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
SQLite3 databases

Related tools

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:

ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.

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:

ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
HMMer finds a hit (regardless of coverage or other bits).

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:

our ignorance of proteins' functions,
omissions in the gene models,
frame-shift errors in the genome sequence, or
the organism lacks the pathway.

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 paper from 2022 on GapMind for carbon sources
the source code
instructions for running GapMind on your computer
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

GapMind for Amino acid biosynthesis