BRENDA - Enzyme Database show
show all sequences of 1.14.13.158

Multienzyme biosynthesis of dihydroartemisinic acid

Chen, X.; Zhang, C.; Too, H.; Molecules 22, 1422-1433 (2017)

Data extracted from this reference:

Application
Application
Commentary
Organism
synthesis
Saccharomyces cerevisiae expressing the native Artemisia annua cytochrome P450 monooxygenase (CYP71AV1) and artemisinic aldehyde D11(13) reductase (DBR2) is used as a whole-cell biocatalyst to produce the immediate artemisinin precursor, dihydroartemisinic acid (DHAA)
Artemisia annua
Cloned(Commentary)
Commentary
Organism
gene cyp71av1, recombinant expression of cytochrome P450 CYP71AV1 in Saccharomyces cerevisiae, coexpression with artemisinic aldehyde D11(13) reductase (DBR2), and artemisinic aldehyde dehydrogenase (ALDH1), which recycles NADPH
Artemisia annua
Engineering
Amino acid exchange
Commentary
Organism
additional information
Saccharomyces cerevisiae expressing the native Artemisia annua cytochrome P450 monooxygenase (CYP71AV1) and artemisinic aldehyde D11(13) reductase (DBR2) is used as a whole-cell biocatalyst to produce the immediate artemisinin precursor, dihydroartemisinic acid (DHAA). Introducing artemisinic aldehyde dehydrogenase (ALDH1) from Artemisia annua, which recycles NADPH, results in a significant enhancement in artemisinate titer. Method optimization and evaluation, host screening and cofactor engineering, overview. The co-expression of DBR2 and modulation of abiotic conditions result in a higher yield. Optimal condition are 80 OD yeast cells in 0.05 ml reaction at pH 8.0. Growing the yeast cells at 20°C in galactose medium increases the dihydroartemisinate titer by 50%
Artemisia annua
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
amorpha-4,11-diene + 3 O2 + 3 NADPH + 3 H+
Artemisia annua
overall reaction, multistep process
artemisinate + 3 NADP+ + 4 H2O
-
-
?
amorpha-4,11-diene + O2 + NADPH + H+
Artemisia annua
-
artemisinic alcohol + NADP+ + H2O
-
-
?
artemisinic alcohol + O2 + NADPH + H+
Artemisia annua
-
artemisinic aldehyde + NADP+ + 2 H2O
-
-
?
artemisinic aldehyde + O2 + NADPH + H+
Artemisia annua
-
artemisinate + NADP+ + H2O
-
-
?
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Artemisia annua
Q1PS23
-
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
amorpha-4,11-diene + 3 O2 + 3 NADPH + 3 H+
overall reaction, multistep process
745821
Artemisia annua
artemisinate + 3 NADP+ + 4 H2O
-
-
-
?
amorpha-4,11-diene + O2 + NADPH + H+
-
745821
Artemisia annua
artemisinic alcohol + NADP+ + H2O
-
-
-
?
artemisinic alcohol + O2 + NADPH + H+
-
745821
Artemisia annua
artemisinic aldehyde + NADP+ + 2 H2O
-
-
-
?
artemisinic aldehyde + O2 + NADPH + H+
-
745821
Artemisia annua
artemisinate + NADP+ + H2O
-
-
-
?
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
recombinant enzyme
Artemisia annua
Cofactor
Cofactor
Commentary
Organism
Structure
cytochrome P450
-
Artemisia annua
heme
a heme catalytic site situated at the C-terminal domain
Artemisia annua
NADPH
-
Artemisia annua
Application (protein specific)
Application
Commentary
Organism
synthesis
Saccharomyces cerevisiae expressing the native Artemisia annua cytochrome P450 monooxygenase (CYP71AV1) and artemisinic aldehyde D11(13) reductase (DBR2) is used as a whole-cell biocatalyst to produce the immediate artemisinin precursor, dihydroartemisinic acid (DHAA)
Artemisia annua
Cloned(Commentary) (protein specific)
Commentary
Organism
gene cyp71av1, recombinant expression of cytochrome P450 CYP71AV1 in Saccharomyces cerevisiae, coexpression with artemisinic aldehyde D11(13) reductase (DBR2), and artemisinic aldehyde dehydrogenase (ALDH1), which recycles NADPH
Artemisia annua
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
cytochrome P450
-
Artemisia annua
heme
a heme catalytic site situated at the C-terminal domain
Artemisia annua
NADPH
-
Artemisia annua
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
additional information
Saccharomyces cerevisiae expressing the native Artemisia annua cytochrome P450 monooxygenase (CYP71AV1) and artemisinic aldehyde D11(13) reductase (DBR2) is used as a whole-cell biocatalyst to produce the immediate artemisinin precursor, dihydroartemisinic acid (DHAA). Introducing artemisinic aldehyde dehydrogenase (ALDH1) from Artemisia annua, which recycles NADPH, results in a significant enhancement in artemisinate titer. Method optimization and evaluation, host screening and cofactor engineering, overview. The co-expression of DBR2 and modulation of abiotic conditions result in a higher yield. Optimal condition are 80 OD yeast cells in 0.05 ml reaction at pH 8.0. Growing the yeast cells at 20°C in galactose medium increases the dihydroartemisinate titer by 50%
Artemisia annua
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
amorpha-4,11-diene + 3 O2 + 3 NADPH + 3 H+
Artemisia annua
overall reaction, multistep process
artemisinate + 3 NADP+ + 4 H2O
-
-
?
amorpha-4,11-diene + O2 + NADPH + H+
Artemisia annua
-
artemisinic alcohol + NADP+ + H2O
-
-
?
artemisinic alcohol + O2 + NADPH + H+
Artemisia annua
-
artemisinic aldehyde + NADP+ + 2 H2O
-
-
?
artemisinic aldehyde + O2 + NADPH + H+
Artemisia annua
-
artemisinate + NADP+ + H2O
-
-
?
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
amorpha-4,11-diene + 3 O2 + 3 NADPH + 3 H+
overall reaction, multistep process
745821
Artemisia annua
artemisinate + 3 NADP+ + 4 H2O
-
-
-
?
amorpha-4,11-diene + O2 + NADPH + H+
-
745821
Artemisia annua
artemisinic alcohol + NADP+ + H2O
-
-
-
?
artemisinic alcohol + O2 + NADPH + H+
-
745821
Artemisia annua
artemisinic aldehyde + NADP+ + 2 H2O
-
-
-
?
artemisinic aldehyde + O2 + NADPH + H+
-
745821
Artemisia annua
artemisinate + NADP+ + H2O
-
-
-
?
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
recombinant enzyme
Artemisia annua
General Information
General Information
Commentary
Organism
metabolism
the first oxidation step by cytochrome P450 (CYP71AV1) is the main rate-limiting step in the dihydroartemisinic acid (DHAA) pathway
Artemisia annua
physiological function
enzyme CYP71AV1 is the critical enzyme that is capable of catalyzing three consecutive oxidation reactions at C-12 position of amorpha-4,11-diene to artemisinate. The heme catalytic site is situated at the C-terminal domain
Artemisia annua
General Information (protein specific)
General Information
Commentary
Organism
metabolism
the first oxidation step by cytochrome P450 (CYP71AV1) is the main rate-limiting step in the dihydroartemisinic acid (DHAA) pathway
Artemisia annua
physiological function
enzyme CYP71AV1 is the critical enzyme that is capable of catalyzing three consecutive oxidation reactions at C-12 position of amorpha-4,11-diene to artemisinate. The heme catalytic site is situated at the C-terminal domain
Artemisia annua
Other publictions for EC 1.14.13.158
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
745821
Chen
Multienzyme biosynthesis of d ...
Artemisia annua
Molecules
22
1422-1433
2017
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1
1
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1
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4
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1
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3
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1
1
3
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1
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4
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4
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1
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2
2
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745905
Chen
Glandular trichome-specific W ...
Artemisia annua
New Phytol.
214
304-316
2017
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1
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4
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1
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1
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1
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4
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1
1
1
1
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746043
Muangphrom
Functional analysis of amorph ...
Artemisia absinthium, Artemisia afra, Artemisia annua, Artemisia kurramensis
Plant Cell Physiol.
57
1678-1688
2016
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3
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4
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8
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3
8
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4
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4
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8
8
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746069
Zheng
-
The influence of endophytic P ...
Artemisia annua
Plant Growth Regul.
80
93-102
2016
-
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1
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1
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1
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1
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1
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1
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1
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746309
Czechowski
Artemisia annua mutant impair ...
Artemisia annua
Proc. Natl. Acad. Sci. USA
113
15150-15155
2016
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1
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4
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1
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4
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6
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2
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1
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4
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6
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3
3
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746035
Ji
Cloning and characterization ...
Artemisia annua
Plant Cell Physiol.
55
1592-1604
2014
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1
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4
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1
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1
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4
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1
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1
1
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4
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1
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4
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1
2
2
1
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