GapMind for Amino acid biosynthesis

 

Definition of L-cysteine biosynthesis

As text, or see rules and steps

# Cysteine biosynthesis in GapMind is based on MetaCyc pathways
# L-cysteine biosynthesis I from serine and sulfide (metacyc:CYSTSYN-PWY),
# II (tRNA-dependent) (metacyc:PWY-6308),
# III from serine and homocysteine (metacyc:HOMOCYSDEGR-PWY),
# V (protein-bound thiocarboxylates) (metacyc:PWY-7289),
# VIII via serine kinase (metacyc:PWY-8009),
# or IX via phosphoserine (metacyc:PWY-8010).
# 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).

# Desulfovibrios have a somewhat diverged serine O-acetyltransferase.
# DVU0662 (uniprot:Q72EB6_DESVH) and DvMF_2657 (uniprot:B8DIT5_DESVM)
# are both essential which suggests that they are correctly annotated.
cysE	serine acetyltransferase	EC:2.3.1.30	uniprot:Q72EB6_DESVH	uniprot:B8DIT5_DESVM

# E. coli also has cysM (same EC number)
cysK	O-acetylserine sulfhydrylase	EC:2.5.1.47

# 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.
from-serine: cysE cysK

# The EC number for these corresponds to homoserine O-succinyltransferase so do not use that.
SST	serine O-succinyltransferase	term:serine O-succinyltransferase
from-serine: SST cysK

CBS	cystathionine beta-synthase	EC:4.2.1.22
# EC:4.4.1.1 includes some other reactions, so it is not used to define CGL.
CGL	cystathionine gamma-lyase	term:cystathionine gamma-lyase
# 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-homocysteine: CBS CGL

sepS	O-phosphoseryl-tRNA ligase	EC:6.1.1.27
pscS	Sep-tRNA:Cys-tRNA synthase	EC:2.5.1.73
# 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-phosphoserine: sepS pscS

Mt_cysM	CysO-thiocarboxylate-dependent cysteine synthase	EC:2.5.1.113
mec	[CysO sulfur-carrier protein]-S-L-cysteine hydrolase	EC:3.13.1.6
moeZ	[sulfur carrier protein CysO]--sulfur ligase	curated:metacyc::G185E-7476-MONOMER
cysO	sulfur carrier protein CysO	curated:SwissProt::P9WP33
from-phosphoserine: cysO moeZ Mt_cysM mec 

# PSSH is similar to cysK or Mt_cysM, so might need ignore clauses?
PSSH	O-phosphoserine sulfhydrylase	EC:2.5.1.65

from-phosphoserine: PSSH

serK	serine kinase (ADP-dependent)	uniprot:Q5JD03
from-serine: serK PSSH

all: from-serine
import ser.steps:serA serC # serA and serC form phosphoserine
all: serA serC from-phosphoserine
all: from-serine-homocysteine

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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