As text, or see rules and steps
# Proline biosynthesis in GapMind is based on MetaCyc pathways # L-proline biosynthesis I from L-glutamate (metacyc:PROSYN-PWY) # and III via L-ornithine aminotransferase (metacyc:PWY-3341). # GapMind also describes proline synthesis via ornithine cyclodeaminase (PMID:11489875). # Pathway II from arginine (metacyc:PWY-4981) should perhaps be included, but is not; # it is reported in nitrogen-fixing cyanobacteria and the bacteria it was reported in also have pathway I. # Pathway IV is not included because it is not reported in prokaryotes (metacyc:PWY-4281). # Also, pathway III is described in MetaCyc as occuring only in plants, but it also is reported # in the archaeon Thermococcus kodakarensis (PMC5846162). import lys.steps:lysW lysZ lysY lysJ lysK # shared with ornithine biosynthesis import arg.steps:ornithine proB glutamate 5-kinase EC:2.7.2.11 # glutamyl-5-phosphate to glutamate 5-semialdehyde, which spontaneously dehydrates to 1-pyrroline-5-carboxylate proA gamma-glutamylphosphate reductase EC:1.2.1.41 # pyrroline-5-carboxylate to proline proC pyrroline-5-carboxylate reductase EC:1.5.1.2 # Pathway I is proBAC. all: proB proA proC # Converts ornithine to glutamate semialdehyde. # CH_124176 is annotated as ornithine transaminase but without the EC number; it probably # has the same activity. OAT L-ornithine 5-aminotransferase EC:2.6.1.13 curated:CharProtDB::CH_124176 # Pathway II involves ornithine aminotransferase (OAT). all: ornithine OAT proC cyclodeaminase ornithine cyclodeaminase EC:4.3.1.12 # Some methanogens synthesize proline via ornithine cyclodeaminase (PMID:11489875). # Unfortunately, the cyclodeaminase has only been linked to sequence in bacteria. all: ornithine cyclodeaminase
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