Information on EC 1.14.99.37 - taxadiene 5alpha-hydroxylase

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The expected taxonomic range for this enzyme is: Taxus

EC NUMBER
COMMENTARY hide
1.14.99.37
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RECOMMENDED NAME
GeneOntology No.
taxadiene 5alpha-hydroxylase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
taxa-4,11-diene + AH2 + O2 = taxa-4(20),11-dien-5alpha-ol + A + H2O
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
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Diterpenoid biosynthesis
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Metabolic pathways
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taxol biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
taxa-4,11-diene,hydrogen-donor:oxygen oxidoreductase (5alpha-hydroxylating)
This microsomal cytochrome-P-450-dependent enzyme is involved in the biosynthesis of the diterpenoid antineoplastic drug Taxol (paclitaxel). The reaction includes rearrangement of the 4(5)-double bond to a 4(20)-double bond, possibly through allylic oxidation.
CAS REGISTRY NUMBER
COMMENTARY hide
253872-99-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
taxa-4(20),11(12)-diene + NADPH + O2
taxa-4(20),11(12)-dien-5alpha-ol + NADP+ + H2O
show the reaction diagram
preferred substrate
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-
?
taxa-4(5),11(12)-diene + NADPH + O2
5(12)-oxa-3(11)-cyclotaxane + NADP+ + H2O
show the reaction diagram
hydroxylation of the C-5alpha is the first of the oxidations resulting in taxol
OCT is a cyclic ether
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?
taxa-4(5),11(12)-diene + NADPH + O2
taxa-4(20),11(12)-dien-5alpha-ol + NADP+ + H2O
show the reaction diagram
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-
?
taxa-4,11-diene + AH2 + O2
taxa-4(20),11-dien-5alpha-ol + A + H2O
show the reaction diagram
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-
?
taxa-4,11-diene + NADPH + O2
taxa-4(20),11-dien-5alpha-ol + NADP+ + H2O
show the reaction diagram
additional information
?
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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
taxa-4(5),11(12)-diene + NADPH + O2
5(12)-oxa-3(11)-cyclotaxane + NADP+ + H2O
show the reaction diagram
Q6WG30
hydroxylation of the C-5alpha is the first of the oxidations resulting in taxol
OCT is a cyclic ether
-
?
taxa-4,11-diene + AH2 + O2
taxa-4(20),11-dien-5alpha-ol + A + H2O
show the reaction diagram
Q6WG30
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-
-
?
taxa-4,11-diene + NADPH + O2
taxa-4(20),11-dien-5alpha-ol + NADP+ + H2O
show the reaction diagram
additional information
?
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Q6WG30
cDNAs encoding taxa-4(5),11(12)-diene synthase and CYP725A4 are introduced in Nicotiana sylvestris for specific expression in trichome cells. The co-expression does not lead to the production of the expected 5-hydroxytaxa-4(20),11(12)-diene. Instead, taxa-4(5),11(12)-diene is quantitatively converted to a novel taxane
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
clotrimazole
cytochrome c
miconazole
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.016
taxa-4(20),11(12)-diene
pH 7.5
0.0069 - 0.024
taxa-4(5),11(12)-diene
0.006
taxa-4,11-diene
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNAs encoding taxa-4(5),11(12)-diene synthase and CYP725A4 are introduced in Nicotiana sylvestris for specific expression in trichome cells. Production of truncated TS in Escherichia coli. The TS cDNA coding for a protein truncated at the N-terminus at amino acid position 75 is cloned in the pET-30b expression vector. Furthermore, CYP725A4 is expressed in yeast.; CYP725A4, DNA and amino acid sequence determination and analysis, expression in the Saccharomyces cerevisiae WAT11 strain containing the Arabidopsis reductase ATR1, and co-expression in Nicotiana sylvestris with taxa-4(5),11(12)-diene synthase, which does not lead to 5alpha-hydroxytaxa-4(20),11(12)-diene, but to formation of 5(12)-oxa-3(11)-cyclotaxane, a tritiated oxidized taxane, structural analysis of the compound, phenotype, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
paclitaxel is a successful anticancer drug
medicine