Definition of chorismate biosynthesis

GapMind for Amino acid biosynthesis

Definition of chorismate biosynthesis

# Chorismate is the starting point for the biosynthesis of the aromatic amino acids
# phenylalanine, tryptophan, and tyrosine.
# Chorismate biosynthesis in GapMind is based on 
# MetaCyc pathways chorismate biosynthesis I (metacyc:ARO-PWY), from
# D-erythrose-4-phosphate and phosphoenolpyruvate, or
# II (metacyc:PWY-6165), from D-glyceraldeyde-3-phosphate and L-asparatate.
# Both pathways are identical after they reach 3-dehydroquinate.

# 4.1.2.15 is an obsolete EC number, but it appears in a few entries.
# This is also known as DAHP (3-deoxy-D-arabino-heptulosonate 7-phosphate) synthase .
# Add Echvi_0120 because it is diverged, is confirmed by cofitness, and is essential in other Bacteroidetes.
# (Echvi_0120 is a fusion with chorismate mutase.)
aroG	3-deoxy-7-phosphoheptulonate synthase	EC:2.5.1.54	uniprot:L0FSZ3_ECHVK	ignore_other:EC 4.1.2.15

# (There's also the obsolete EC number 4.6.1.3, no longer used.)
aroB	3-dehydroquinate synthase	EC:4.2.3.4

aroD	3-dehydroquinate dehydratase	EC:4.2.1.10

# EC:1.1.1.282 is with NAD(P)H instead of NADPH.
# Manually add the B. theta gene (BT4215, uniprot:Q8A006_BACTN) because it is diverged, is the only good candidate,
# and is essential in various Bacteroidetes
aroE	shikimate dehydrogenase	EC:1.1.1.25	EC:1.1.1.282	uniprot:Q8A006_BACTN

# In E. coli, AroL and AroK are isozymes.
# In Bacillus subtilis, this gene was known as AroI, and it was cloned by complementation
# (see A. Nakane et al, J. Fermentation and Bioengineering 1994, 77:312-314.)
# That sequence is identical to uniprot:AROK_BACSU.
# Manually add BT3393 (uniprot:AROK_BACTN) from B. thetaiotaomicron because it is diverged, is the only good candidate,
# and is essential in various Bacteroidetes.
# Similarly for Echvi_0140 (uniprot:L0FT15_ECHVK) from Echinicola vietnamensis.
# And DVU0892 (uniprot:AROK_DESVH) from D. vulgaris Hildenborough is confirmed by cofitness
# CCNA_03103 (uniprot:AROK_CAUVN) is confirmed by cofitness and similar proteins
# such as SMc00695 (uniprot:AROK_RHIME) and PGA1_c14090 (uniprot:I7EWF3_PHAIB) are essential.
aroL	shikimate kinase	EC:2.7.1.71	uniprot:AROK_BACSU	uniprot:AROK_BACTN	uniprot:L0FT15_ECHVK	uniprot:AROK_DESVH	uniprot:AROK_CAUVN	uniprot:AROK_RHIME	uniprot:I7EWF3_PHAIB

# Add AroA from Desulfovibrio vulgaris (DVU0463) because it is a bit diverged, is conserved essential,
# and clusters with aromatic amino acid biosynthesis genes
aroA	3-phosphoshikimate 1-carboxyvinyltransferase	EC:2.5.1.19	uniprot:Q72EV5_DESVH

# (There's also obsolete EC 4.6.1.4, no longer used)
aroC	chorismate synthase	EC:4.2.3.5

# The triose-phosphate isomerase tpiA is also thought to convert D-glyceraldehyde 3-phosphate to enolaldehyde, which
# spontaneously converts to methylglyoxal.
# (Alternatively, methylglyoxal might be formed by methylgyoxal synthase, EC 4.2.3.3?)
tpiA	D-glyceraldehyde-3-phosphate phospholyase	EC:5.3.1.1

# 6-deoxy-5-ketofructose-1-phosphate synthase is an activity of some fructose-bisphosphate aldolases
# (which are usually annotated as 4.1.2.13). To find the fbp in Desulfovibrio vulgaris Hildenborough
# and Miyazaki F, it is necessary to match more broadly.
# And ignore CharProtDB items with incorrect EC.
fbp	6-deoxy-5-ketofructose 1-phosphate synthase	EC:2.2.1.11	EC:4.1.2.13	ignore_other:fructose%bisphosphate aldolase

import met.steps:aspartate-semialdehyde

# aroA' condenses 6-deoxy-5-ketofructose 1-phosphate with L-aspartate 4-semialdehyde
aroA'	2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate synthase	EC:2.2.1.10

aroB'	dehydroquinate synthase II	EC:1.4.1.24

# Pathway I uses aroG and aroB, while pathway II uses non-canonical activities of triose-phosphate
# isomerase (tpiA) and fructose-bisphosphate aldolase (fbp)
# to form 6-deoxy-5-ketofructose 1-phosphate. AroA' condenses this with asparate semialdehyde
# to 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate,
# and AroB' cyclizes it to 3-dehydroquinate.
3-dehydroquinate: aroG aroB
3-dehydroquinate: tpiA fbp aspartate-semialdehyde aroA' aroB'

all: 3-dehydroquinate aroD aroE aroL aroA aroC

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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, 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

GapMind for Amino acid biosynthesis