GapMind for Amino acid biosynthesis

 

Definition of L-tryptophan biosynthesis

As text, or see rules and steps

# Tryptophan biosynthesis in GapMind is based on MetaCyc pathway
# L-tryptophan biosynthesis (metacyc:TRPSYN-PWY), from chorismate,
# glutamine, 5-phosphoribose-1-diphosphate, and serine.

# This component of anthranilate synthase is also known as the alpha subunit  or component I.
# BT0532 (uniprot:Q8AAD3_BACTN) and CA265_RS22890 (uniprot:A0A1X9ZB07_9SPHI) are also component I.
# Similarly for DVU0465 (uniprot:Q72EV3_DESVH) and DvMF_1746 (uniprot:B8DM47_DESVM).
# Some related proteins have EC:2.6.1.85 which should perhaps be ignored.
trpE	anthranilate synthase subunit TrpE	hmm:TIGR00564	hmm:TIGR00565	hmm:TIGR01820	term:anthranilate synthase component 1	term:anthranilate synthase component I	term:anthranilate synthase alpha subunit	uniprot:Q8AAD3_BACTN	uniprot:A0A1X9ZB07_9SPHI	uniprot:Q72EV3_DESVH	uniprot:B8DM47_DESVM	ignore_other:EC 4.1.3.27

# This component of anthranilate synthase is also known as the beta subunit or component II.
# Note that E. coli TrpD is this component fused to anthranilate phosphoribosyltransferase
# (which is described separately).
# Some proteins are components of both anthranilate synthase and 4-amino-4-deoxychorismate synthase (EC:2.6.1.85).
# Similarly, TIGR00566 also matches the amidotransferase component of para-aminobenzoate synthase.
# BT0531 (uniprot:Q8AAD4_BACTN) and CA265_RS22895 (uniprot:A0A1X9ZDE4_9SPHI) are also component II
# Similarly for DVU0466 (uniprot:Q72EV2_DESVH) and DvMF_1745 (uniprot:B8DM46_DESVM).
trpD_1	glutamine amidotransferase of anthranilate synthase	hmm:TIGR00566	term:anthranilate synthase component 2	term:anthranilate synthase component II	term:anthranilate synthase beta subunit	uniprot:Q8AAD4_BACTN	uniprot:A0A1X9ZDE4_9SPHI	uniprot:Q72EV2_DESVH	uniprot:B8DM46_DESVM	ignore_other:EC 4.1.3.27	ignore_other:EC 2.6.1.85

# Often fused to anthranilate synthase so ignore that (i.e., P00500 is labeled in BRENDA as
# a subunit of anthranilate synthase; it is probably anthranilate phosphoribosyltransferase as well)
trpD_2	anthranilate phosphoribosyltransferase	EC:2.4.2.18	ignore_other:EC 4.1.3.27

# Some alphaproteobacteria have a single-protein anthranilate synthase
trpED	anthranilate synthase, alpha proteobacterial clade	hmm:TIGR01815	ignore_other:EC 4.1.3.27

# PRAI is sometimes known as trpF or as part of trpC (if fused to IGPS).
# In Bacteroides thetaiotaomicron, BT0528 (uniprot:Q8AAD7_BACTN) has a PRAI domain (pfam:PF00697), is auxotrophic,
# and clusters with trp synthesis genes
# Similarly, annotate CCNA_03659 (uniprot:A0A0H3CC53_CAUVN), SMc02767 (uniprot:TRPF_RHIME),
# and Ga0059261_0237 (uniprot:A0A1L6JC25_9SPHN).
# Some bacteria have a bifunctional phosphoribosylanthranilate isomerase (EC 5.3.1.24)
# and isomerase in histidine biosynthesis (hisA, EC:5.3.1.16), for instance uniprot:P16250.
# (In both reactions a N-modified-1-amino-ribofuranose-5-phosphate rearranges to a
#  linear N-modified-1-amino-ribulose-5-phosphate.)
# So hits to hisA are ignored.
PRAI	phosphoribosylanthranilate isomerase	EC:5.3.1.24	uniprot:Q8AAD7_BACTN	uniprot:A0A0H3CC53_CAUVN	uniprot:TRPF_RHIME	uniprot:A0A1L6JC25_9SPHN	ignore_other:EC 5.3.1.16

# Sometimes fused to anthranilate synthase subunits or known as trpC (if fused to PRAI).
# Ignore BRENDA::P24920 because annotated as phosphoribosylanthranilate isomerase but is also believed to be IGPS.
# And based on presence in Trp clusters and auxotrophic or cofit phenotypes, annotate somewhat diverged IGPS:
# HP15_3291 (uniprot:E4PQZ8_MARAH), DvMF_1743 (uniprot:B8DM44_DESVM), BT0529 (uniprot:TRPC_BACTN),
# AZOBR_RS07450 (uniprot:G8AL05_AZOBR), Pf1N1B4_2549 (uniprot:A0A166NT80_PSEFL), AO353_07210 (uniprot:A0A0N9WG05_PSEFL).
IGPS	indole-3-glycerol phosphate synthase	EC:4.1.1.48	uniprot:E4PQZ8_MARAH	uniprot:B8DM44_DESVM	uniprot:TRPC_BACTN	uniprot:G8AL05_AZOBR	uniprot:A0A166NT80_PSEFL	uniprot:A0A166NT80_PSEFL	ignore_other:EC 4.1.3.27	ignore:BRENDA::P24920

# This reaction is 4.1.2.8 by itself or part of 4.2.1.20
trpA	indoleglycerol phosphate aldolase	hmm:TIGR00262	ignore_other:EC 4.2.1.20	ignore_other:EC 4.1.2.8

# Some members of TIGR01415 might also have this activity.
# The family also includes indole-scavenging "trpB-2" proteins, whose presence generally indicates
# tryptophan synthesis (EC 4.2.1.122)
trpB	tryptophan synthase	hmm:TIGR00263	ignore_other:EC 4.2.1.20	ignore_other:EC 4.2.1.122

# Anthranilate synthase usually has two components, as in E. coli, but single-protein systems are also known.
# (In E. coli, trpD is the second component fused to anthranilate phosphoribosyltransferase.) 
anthranilate-synthase: trpE trpD_1
anthranilate-synthase: trpED

all: anthranilate-synthase trpD_2 PRAI IGPS trpA trpB

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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, 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