Definition of glycine biosynthesis

GapMind for Amino acid biosynthesis

Definition of glycine biosynthesis

# 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).
# Also, glyXS:glyXL is regulated by a glycine riboswitch in Bacillus methanolicus (see BMMGA3_03000 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

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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:

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