Definition of L-threonine biosynthesis

GapMind for Amino acid biosynthesis

Definition of L-threonine biosynthesis

# Threonine biosynthesis in GapMind is based on MetaCyc pathway
# L-threonine biosynthesis (metacyc:HOMOSER-THRESYN-PWY).

import met.steps:homoserine

# ThrB from B. subtilis (uniprot:P04948) can complement a thrB- strain of E. coli (PMC1167255; Bradley Biggs).
thrB	homoserine kinase	EC:2.7.1.39	uniprot:P04948

# BT2402 (uniprot:Q8PX04) is required for threonine synthesis (PMC7311316) and belongs to a family
# (TIGR02535) that was proposed replace the missing homoserine kinase. It is
# often encoded next to aspartate kinase and threonine synthase.
# It is related to phosphoglycerate mutases and might transfer phosphate groups
# from a donor such as phosphoenolpyruvate to homoserine.
# This family is also known as ThrB2 (PMC9026213).
# In GapMind, HomK is described separately from ThrB because it probably carries out a different reaction.
homK	putative homoserine phosphotransferase	predicted:Q8PX04

# N515DRAFT_0575 (uniprot:A0A1I2JHD2_9GAMM) from Dyella japonica UNC79MFTsu3.2 is somewhat
# diverged; mutants in this gene are auxotrophic.
thrC	threonine synthase	EC:4.2.3.1	uniprot:A0A1I2JHD2_9GAMM

all: homoserine thrB thrC
all: homoserine homK thrC

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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