GapMind for Amino acid biosynthesis

 

Definition of L-proline biosynthesis

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

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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 against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer. 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. 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 the paper from 2019 on GapMind for amino acid biosynthesis, the preprint on GapMind for carbon sources, or view the source code, or see 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