As text, or see rules and steps
# Glycine biosynthesis in GapMind is based on MetaCyc pathways # glycine biosynthesis I from serine (metacyc:GLYSYN-PWY), # III from glyoxylate (metacyc:GLYSYN-ALA-PWY), # or IV from threonine (metacyc:GLYSYN-THR-PWY). # Pathway II from methylene-tetrahydrofolate, CO2, and ammonia # (metacyc:GLYSYN-PWY) is not included because it is not clear that bacteria really # run this in reverse (although apparently budding yeast can). # Glcyine synthiesis by glyXL/glyXS, whose biochemical function is not known, is also represented. # Another pathway not listed is the formation of glycine from glycolate # as in Pelagibacter (see PMID:23096402). This is an unusual nutritional requirement. # Some methanogens use tetrahydromethanopterin instead of tetrahydrofolate as the folate carrier, # which is annotated as "Serine hydroxymethyltransferase" but with a different EC number. glyA serine hydroxymethyltransferase EC:2.1.2.1 term:Serine hydroxymethyltransferase # CH_123497 is isocitrate lyase but is annotated without the EC number. # uniprot:Q05957 is misannotated in BRENDA as this function; it prefers other substrates (PMID:16342929) # uniprot:P28467 is annotated as this by two resources but is only 15 amino acids, so it is ignored. aceA isocitrate lyase EC:4.1.3.1 curated:CharProtDB::CH_123497 ignore:BRENDA::Q05957 ignore:SwissProt::P28467 # uniprot:P84188 and uniprot:P84187 are ignored because they appear to be sequence fragments # and do not contain the full aminotransferase domain agx1 alanine--glyoxylate aminotransferase EC:2.6.1.44 ignore:SwissProt::P84188 ignore:SwissProt::P84187 # E. coli serA (uniprot:P0A825) is annotated in BRENDA as threonine aldolase, but other resources # report that it is active on allothreonine only. # CH_123166 is L-threonine aldolase but was annotated without the EC number, so it is added manually. # uniprot:O07051 is ignored because it specific for L-allothreonine. gly1 L-threonine aldolase EC:4.1.2.5 EC:4.1.2.48 ignore:BRENDA::P0A825 curated:CharProtDB::CH_123166 ignore:SwissProt::O07051 # Glycine synthesis by Bifidobacterium breve or Methanococcus maripaludis requires two genes: # a putative enzyme (distantly related to anaerobic ribonucleotide reductase), which we call glyXL, and an ACT domain protein, # which we call glyXS (BBR_RS12920 and BBR_RS12915 or MMP_RS07345 and MMP_RS03450, Anthony Shiver and Leslie Day). # These proteins are usually encoded next to each other (although not in Methanococcus). # A homolog of glyXL from Streptococcus (spr0218, uniprot:Q8DRD2) is also required for glycine synthesis (PMC2739083). # And a similar operon is regulated by glycine riboswitches (see BMMGA3_03000, discussed in PMC4342826). glyXL putative glycine synthesis enzyme, catalytic component uniprot:Q8G510 uniprot:Q6LXC5 uniprot:Q8DRD2 # Required for glycine synthesis along with glyXL in Bifodobacterium breve and Methanococcus maripaludis. # ACT domain proteins often bind amino acids to regulate the activity of enzymes, so we # predict that glyXL is the catalytic component. glyXS putative glycine synthesis enzyme, ACT domain component uniprot:Q8G509 uniprot:Q6LZH1 from_serine: glyA # For biosynthesis from glyoyxlate (pathway III), assume that the glyoxylate is formed from # isocitrate (an intermediate in the TCA cycle). via_glyoxylate: aceA agx1 from_threonine: gly1 all: from_serine all: via_glyoxylate all: from_threonine all: glyXL glyXS
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