Information on EC 4.2.3.4 - 3-dehydroquinate synthase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY hide
4.2.3.4
-
RECOMMENDED NAME
GeneOntology No.
3-dehydroquinate synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate = 3-dehydroquinate + phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
aldol condensation
-
intramolecular
cyclization
elimination
-
-
P-O bond cleavage
-
oxidation
-
alcohol oxidation
reduction
-
carbonyl reduction
additional information
-
DHQS itself is of interest because it apparently catalyzes five individual reactions, alcohol oxidation, phosphate omega-elimination, carbonyl reduction, ring opening and intramolecular aldol condensation, in a single active site as well as being a drug target
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3-dehydroquinate biosynthesis I
-
-
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
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chorismate metabolism
-
-
Metabolic pathways
-
-
Phenylalanine, tyrosine and tryptophan biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
3-deoxy-D-arabino-hept-2-ulosonate-7-phosphate phosphate-lyase (cyclizing; 3-dehydroquinate-forming)
Requires Co2+ and bound NAD+. The hydrogen atoms on C-7 of the substrate are retained on C-2 of the product.
CAS REGISTRY NUMBER
COMMENTARY hide
37211-77-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Hansenula henricii
-
-
-
Manually annotated by BRENDA team
pea
-
-
Manually annotated by BRENDA team
Rhodosporidium sphaerocarpum
-
-
-
Manually annotated by BRENDA team
Rhodosporidium toruloides
-
-
-
Manually annotated by BRENDA team
Saccharomycopsis lipolytica
-
-
-
Manually annotated by BRENDA team
Sorghum sp.
-
-
-
Manually annotated by BRENDA team
strain HB8
Uniprot
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
the enzyme catalyses the second step of the shikimate pathway to aromatic compounds
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(3R)-3-fluoro-3-deoxy-D-arabino-heptulosonate 7-phosphate
(6R)-6-fluoro-dehydroquinate
show the reaction diagram
(3S)-3-fluoro-3-deoxy-D-arabino-heptulosonate 7-phosphate
(6S)-6-fluoro-dehydroquinate + 1-epi-(6S)-6-fluoro-dehydroquinate
show the reaction diagram
3-deoxy-arabino-heptulonate 7-phosphate
3-dehydroquinate + phosphate
show the reaction diagram
-
-
-
-
?
3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate
3-dehydroquinate + phosphate
show the reaction diagram
3-deoxy-D-arabino-heptulosonate 7-phosphate
3-dehydroquinate + phosphate
show the reaction diagram
3-deoxy-D-arabino-heptulosonic acid 7-phosphate
3-dehydroquinate + phosphate
show the reaction diagram
3-deoxy-D-arabino-heptulosonic acid 7-phosphate
?
show the reaction diagram
3-deoxy-D-arabinoheptulosonate 7-phosphate
3-dehydroquinate + phosphate
show the reaction diagram
-
shikimate pathway is present in all organisms except mammals
-
-
?
additional information
?
-
-
enzyme plays an essential role in the synthesis of aromatic compounds in the shikimate pathway
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-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate
3-dehydroquinate + phosphate
show the reaction diagram
3-deoxy-D-arabino-heptulosonate 7-phosphate
3-dehydroquinate + phosphate
show the reaction diagram
P56081
second key step in the shikimate pathway which is crucial for the aromatic amino acid metabolism in bacteria, fungi, and plants, but not in mammals
-
-
?
3-deoxy-D-arabino-heptulosonic acid 7-phosphate
?
show the reaction diagram
3-deoxy-D-arabinoheptulosonate 7-phosphate
3-dehydroquinate + phosphate
show the reaction diagram
-
shikimate pathway is present in all organisms except mammals
-
-
?
additional information
?
-
-
enzyme plays an essential role in the synthesis of aromatic compounds in the shikimate pathway
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-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
no cofactor: NADP+
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
-
110% of the activity in presence of Co2+
Ni2+
-
reconstitution of the apoenzyme with Ni2+ restores activity to 23% of the level observed with the Co2+-holoenzyme
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(-)-epicatechin gallate
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-
(-)-epigallocatechin gallate
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-
1,10-phenanthroline
-
-
3-deoxy-D-arabino-heoptulosonic acid
-
-
3-deoxy-D-arabino-heptulosonic acid 7-homophosphate
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-
-
3-deoxy-D-arabino-heptulosonic acid 7-phosphonate
3-deoxy-D-arabino-heptulosonic acid-2-O-methylglycoside 7-phosphate
-
-
-
alpha-(2,6-anhydro-3-deoxy-D-arabino-heptulopyranosid)onate 7-phosphate
alpha-(2,6-anhydro-3-deoxy-D-arabino-heptulopyranosid)onate 7-phosphonate
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-
beta-(2,6-anhydro-3-deoxy-D-arabino-heptulopyranosid)onate 7-phosphate
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-
bistrispropane
-
-
carabaphosphonate
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-
D-2-cis-hydroquinic acid
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-
D-gluco-3-heptulosonate 7-phosphate
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D-gluco-heptulosonate 7-homophosphonate
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D-gluco-heptulosonate 7-phosphonate
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diethyl dicarbonate
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dithiothreitol
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epoxyshikimic acid
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gallic acid
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[(1R)-(1alpha,3beta,4alpha ,5beta)]-5-(2-phosphonoethyl)-1,3,4-trihydroxycyclohexane-1-carboxylic acid
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[(1R)-(1alpha,3beta,4alpha,5beta)]-1,4,5-trihydroxy-3-(phosphonooxy)-cyclohexane-1-carboxylate
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[(1R)-(1alpha,3beta,4alpha,5beta)]-5-(E)-(2-phosphonoethenyl)-1,3,4-trihydroxycyclohexane-1-carboxylic acid
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[(1R)-(1alpha,3beta,4alpha,5beta)]-5-(phosphonomethyl)-1,3,4-trihydroxycyclohexane-1-carboxylic acid
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slow binding inhibitor
[(1R)-(1alpha,3beta,4alpha,5beta)]-5-(Z)-(2-phosphonoethenyl)-1,3,4-trihydroxycyclohexane-1-carboxylic acid
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[(2R)-(2alpha,4beta,5alpha,6beta)]-6-(2-phosphonoethyl)-2,4,5-trihydroxytetrahydropyran-2-carboxylate
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[(2R)-(2alpha,4beta,5alpha,6beta)]-6-(phosphonomethyl)-2,4,5-trihydroxytetrahydropyran-2-carboxylate
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-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD+
binding on the N-terminal alpha/beta domain
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0016 - 0.0087
(3R)-3-fluoro-3-deoxy-D-arabino-heptulosonate 7-phosphate
0.021 - 0.064
(3S)-3-fluoro-3-deoxy-D-arabino-heptulosonate 7-phosphate
0.00055 - 1.3
3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate
0.021 - 0.228
3-deoxy-D-arabino-heptulosonate 7-phosphate
0.0022
3-deoxy-D-arabino-heptulosonate phosphate
-
-
0.0014 - 0.055
3-deoxy-D-arabino-heptulosonic acid 7-phosphate
0.0019 - 0.055
NAD+
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.3 - 3.3
(3R)-3-fluoro-3-deoxy-D-arabino-heptulosonate 7-phosphate
0.9 - 1.3
(3S)-3-fluoro-3-deoxy-D-arabino-heptulosonate 7-phosphate
0.5 - 25000
3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate
6.8
3-deoxy-D-arabino-heptulosonate 7-phosphate
Aspergillus nidulans
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-
19
3-deoxy-D-arabino-heptulosonic acid 7-phosphate
Neurospora crassa
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-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
34.5 - 1650
(3R)-3-fluoro-3-deoxy-D-arabino-heptulosonate 7-phosphate
14 - 44.8
(3S)-3-fluoro-3-deoxy-D-arabino-heptulosonate 7-phosphate
156 - 2807
3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000008
CBP
contains 5 functional groups (OH, COOH and phosphate)
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.061
HTS 11955
Helicobacter pylori
P56081
in 100 mM DMSO, compound carries N or O atoms and functional groups (CN, NH2 and NO2)
0.0845
RH 00573
Helicobacter pylori
P56081
in 100 mM DMSO, compound carries N or O atoms and functional groups (CN, NH2 and NO2)
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.009
strain NR7, plasmid pKL4.79, activity is measured for cells removed from the fermentor 24 h after inoculation
0.01
strain NR7, plasmid pKL4.79, activity is measured for cells removed from the fermentor 36 h after inoculation
0.011
strain NR7, plasmid pKL4.79, activity is measured for cells removed from the fermentor 48 h after inoculation
0.015
strain NR7, plasmid pNR8.075, activity is measured for cells removed from the fermentor 24 h after inoculation
0.016
strain NR7, plasmid pNR8.075, activity is measured for cells removed from the fermentor 36 h after inoculation; strain NR7, plasmid pNR8.075, activity is measured for cells removed from the fermentor 48 h after inoculation; strain NR7, plasmid pNR8.288, activity is measured for cells removed from the fermentor 48 h after inoculation
0.017
strain NR7, plasmid pNR8.288, activity is measured for cells removed from the fermentor 24 h after inoculation; strain NR7, plasmid pNR8.288, activity is measured for cells removed from the fermentor 36 h after inoculation
0.022
strain NR7, plasmid pNR9.127, activity is measured for cells removed from the fermentor 36 h after inoculation
0.023
strain NR7, plasmid pNR8.294, activity is measured for cells removed from the fermentor 48 h after inoculation
0.024
strain NR7, plasmid pNR9.127, activity is measured for cells removed from the fermentor 48 h after inoculation
0.027
strain NR7, plasmid pNR9.127, activity is measured for cells removed from the fermentor 24 h after inoculation
0.039
strain NR7, plasmid pNR8.294, activity is measured for cells removed from the fermentor 36 h after inoculation
0.043
strain NR7, plasmid pNR8.294, activity is measured for cells removed from the fermentor 24 h after inoculation
0.07
-
mutant R130K
0.53
strain NR7, plasmid pNR9.056, activity is measured for cells removed from the fermentor 24 h after inoculation
0.92
strain NR7, plasmid pNR9.056, activity is measured for cells removed from the fermentor 36 h after inoculation
1.17
strain NR7, plasmid pNR9.056, activity is measured for cells removed from the fermentor 48 h after inoculation
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.5
Sorghum sp.
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-
7.4 - 8.4
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7.5
activity assay
7.6
-
activity assay
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.3 - 9.5
pH 6.3: 65% of maximal activity, pH 9.5: about 65% of maximal activity
6.8 - 8
Sorghum sp.
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-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
activity assay
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Helicobacter pylori (strain ATCC 700392 / 26695)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Staphylococcus aureus (strain MRSA252)
Staphylococcus aureus (strain MRSA252)
Staphylococcus aureus (strain MRSA252)
Staphylococcus aureus (strain MRSA252)
Staphylococcus aureus (strain MRSA252)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
24000
-
enzyme complex with chorismate synthase, SDS-PAGE
38100
-
determined by SDS-PAGE
38140
-
determined by ESI-MS
40000 - 44000
-
HPLC
44000
-
HPLC
57000
-
gel filtration
66000
-
gel filtration
67000
-
gel filtration
72000
gel filtration
78400
dynamic light scattering method, bimodal analysis
79200
-
light scattering
81000
-
gel filtration
290000 - 330000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
monomer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
molecular replacement based on the structure of Aspergillus nidulans enzyme, PDB code 1NR5, revealing a homodimeric protein. Each monomer has a NAD+ binding site nestled between the distinct N- and C-terminal domains
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sitting-drop vapour-diffusion crystallisation at 4C utilising microbridges, crystals of unliganded enzyme as well as in complexes with NAD+, the substrate analogue [1R-(1alpha,3beta,4alpha,5beta)]-5-phosphonomethyl-1,3,4-trihydroxycyclohexane-1-carboxylic acid and together with both, NAD+ and [1R-(1alpha,3beta,4alpha,5beta)]-5-phosphonomethyl-1,3,4-trihydroxycyclohexane-1-carboxylic acid
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sitting-drop vapour-diffusion, crystals of unliganded enzyme, binary complexes with either the substrate analogue, carbaphosphonate or the cofactor NADH, as well as the ternary enzyme-carbaphosphonate-cofactor complex
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sitting-drop vapour-diffusion, structure at 1.7 A resolution
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obtained in a solution containing 20 mM NAD+
sitting-drop vapour-diffusion crystallisation at 4C utilising microbridges, crystals of unliganded enzyme as well as in complexes with NAD, the substrate analogue [1R-(1alpha,3beta,4alpha,5beta)]-5-phosphonomethyl-1,3,4-trihydroxycyclohexane-1-carboxylic acid and together with both, NAD and [1R-(1alpha,3beta,4alpha,5beta)]-5-phosphonomethyl-1,3,4-trihydroxycyclohexane-1-carboxylic acid
oil microbatch method, homodimer 1.8 A resolution
by using the hanging-drop vapour-diffusion method with different screening kits, yields crystals belonging to the tetragonal space group, crystals of DHQS obtained in sitting-drop setups using a hydra automated high-throughput crystal screening machine with different screening kits: (a) 0.1 M sodium malonate pH 4.0, 12% PEG 3350, (b) 0.2 M sodium malonate pH 6.0, 20% PEG 3350, (c) 0.1 M Tris pH 8.5, 2.0 M ammonium sulfate, (d) 0.15 M caesium chloride, 15% PEG 3350, (e) 1.0 M sodium citrate, 0.1 M CHES pH 9.5, (f) 0.2 M ammonium sulfate, 0.1 M bis-Tris pH 5.5, 25% PEG 3350, (g) 0.2 M ammonium sulfate, 0.1 M MES pH 6.5, 30% PEG MME 5000, (h) 0.02 M zinc chloride, 20% PEG 3350. Best crystals are obtained after two weeks from a reservoir containing 0.2 M ammonium sulfate, 0.1 M MES monohydrate pH 6.0 and 31%PEG MME 5000
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
-20
-
inactivation
4
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48 h, 65% activity
41
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melting temperature, in presence of either Zn2+ or Co2+
45
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3-deoxy-D-arabino-heptulosonate protects against inactivation
55
-
inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
freezing and thawing , inactivation
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, more than 1 year
-
-70C, more than 1 year
-
1 month
-
4C, free enzyme in the presence of Co2+ and NAD+, at pH 7.5 in 100 mM MOPS buffer, several months, the enzyme remains stable
-
50% glycerol
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
arom-multienzyme complex
-
by Ni2+-NTA affinity chromatography, enzyme is subjected to a TEV protease cleavage reaction to cleave the six His-tag residues at the N-terminus, further purification by ion-exchange chromatography
-
expressed HpDHQS protein is purified by immobilized nickel-ion chromatography
partial
together with chorismate synthase
-
using a Q-Sepharose Fast Flow, a HiLoad 16/10 phenyl-Sepharose, and a Sephacryl S-200 HR column
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli BL21
into the pET23a+ vector for expression in Escherichia coli BL21DE3 cells
-
overexpressed in Escherichia coli Rosetta DE3. The enzyme is insoluble when expressed in Escherichia coli but is partially solubilised when KCl is included in the cell lysis buffer
overexpression in Escherichia coli
-
overexpression of the dehydroquinate synthase domain of the pentafunctional AROM protein in Escherichia coli
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The aroB gene cloned from Xoo and the corresponding DHQS protein is subsequently overexpressed in Escherichia coli
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The aroB gene encoding HpDHQS is amplified from genomic DNA by PCR and inserted into the pQE30 expression vector. The HpDHQS protein is expressed from Escherichia coli JM109 cells transformed with pQE30-HpDHQS
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
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