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
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:
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