GapMind for Amino acid biosynthesis

 

Definition of L-histidine biosynthesis

As text, or see rules and steps

# Histidine biosynthesis in GapMind is based on the MetaCyc pathway (metacyc:HISTSYN-PWY).

prs	ribose-phosphate diphosphokinase	EC:2.7.6.1
hisG	ATP phosphoribosyltransferase	EC:2.4.2.17
# Genetic evidence suggests that DVU1186 (uniprot:Q72CU7_DESVH) is phosphoribosyl-ATP pyrophosphatase (PMC5764234).
# CH_123581 probably does all three: hisD, hisE, and hisI.
hisI	phosphoribosyl-ATP pyrophosphatase	EC:3.6.1.31	uniprot:Q72CU7_DESVH	ignore:CharProtDB::CH_123581
hisE	phosphoribosyl-AMP cyclohydrolase	EC:3.5.4.19	hmm:PF01502	ignore:CharProtDB::CH_123581
hisA	isomerase HisA	EC:5.3.1.16
hisF	IGP synthase, cyclase subunit	term:hisF	hmm:TIGR00735	ignore_other:imidazole glycerol phosphate synthase
hisH	IGP synthase, amidotransferase subunit	term:hisH	hmm:TIGR01855	ignore_other:imidazole glycerol phosphate synthase
# Fitness data showed that BPHYT_RS17700 (B2SZ63) from Burkholderia phytofirmans is required for histidine biosynthesis.
# PA5143 (Q9HU41) from Pseudomonas aeruginosa is required for histidine biosynthesis (PMC7028973).
# as 
hisB	IGP dehydratase	EC:4.2.1.19	uniprot:B2SZ63	uniprot:Q9HU41

# In Bacillus subtilis, the histidinol-phosphate aminotransferase activity is provided by a gene that is in a cluster of
# genes for tyrosine and phenylalanine biosynthesis (PMID:4431). Homology suggests that this
# activity is provided by "HisH" (BSU22620), which indeed is just upstream of tyrA (PMID:6092865).
# This protein is now usually referred to as "HisC" (uniprot:HIS8_BACSU)
hisC	histidinol-phosphate aminotransferase	EC:2.6.1.9	uniprot:HIS8_BACSU

# In Bacillus subtilis and some related bacteria, histidinol-phosphate phosphatase is known as HisJ
# and has been confirmed by biochemical assays of purified proteins (PMC3570733).
# The identifiers given (see their Table 3) are
# MCCL_0344 BBR47_00270 BCE_1533 BcerKBAB4_1335 BcerKBAB4_1335 BSU29620 BH3206 GK2799 SMU_1486c
# (uniprot:B9E9Z0_MACCJ uniprot:C0ZH63_BREBN uniprot:Q73B87_BACC1 uniprot:A9VLI0_BACWK uniprot:HIS9_BACHD
# uniprot:Q5KW52_GEOKA uniprot:Q8DT80_STRMU uniprot:HIS9_BACSU).
hisN	histidinol-phosphate phosphatase	EC:3.1.3.15	uniprot:B9E9Z0_MACCJ	uniprot:C0ZH63_BREBN	uniprot:Q73B87_BACC1	uniprot:A9VLI0_BACWK	uniprot:HIS9_BACHD	uniprot:Q5KW52_GEOKA	uniprot:Q8DT80_STRMU	uniprot:HIS9_BACSU

hisD	histidinol dehydrogenase	EC:1.1.1.23	ignore:CharProtDB::CH_123581

all: prs hisG hisI hisE hisA hisF hisH hisB hisC hisN hisD

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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