Information on EC 1.14.99.14 - progesterone 11alpha-monooxygenase

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

EC NUMBER
COMMENTARY hide
1.14.99.14
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RECOMMENDED NAME
GeneOntology No.
progesterone 11alpha-monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
progesterone + AH2 + O2 = 11alpha-hydroxyprogesterone + A + H2O
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Steroid hormone biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
progesterone,hydrogen-donor:oxygen oxidoreductase (11alpha-hydroxylating)
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CAS REGISTRY NUMBER
COMMENTARY hide
37256-77-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain G8
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Manually annotated by BRENDA team
strain NRRL 405
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Manually annotated by BRENDA team
gene CYP509C12
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Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
11-deoxycorticosterone + AH2 + O2
? + A + H2O
show the reaction diagram
11-deoxycortisol + AH2 + O2
? + A + H2O
show the reaction diagram
11alpha-hydroxyprogesterone + NADPH + O2
6beta,11alpha-dihydroxyprogesterone
show the reaction diagram
19-nortestosterone + NADPH + O2
11alpha-hydroxy-19-nortestosterone + NADP+ + H2O
show the reaction diagram
progesterone + AH2 + O2
11alpha-hydroxyprogesterone + A + H2O
show the reaction diagram
progesterone + NADPH + O2
11alpha-hydroxyprogesterone + NADP+ + H2O
show the reaction diagram
testosterone + AH2 + O2
11alpha-hydroxytestosterone + A + 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
11-deoxycorticosterone + AH2 + O2
? + A + H2O
show the reaction diagram
11-deoxycortisol + AH2 + O2
? + A + H2O
show the reaction diagram
progesterone + AH2 + O2
11alpha-hydroxyprogesterone + A + H2O
show the reaction diagram
progesterone + NADPH + O2
11alpha-hydroxyprogesterone + NADP+ + H2O
show the reaction diagram
testosterone + AH2 + O2
11alpha-hydroxytestosterone + A + H2O
show the reaction diagram
additional information
?
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Q06069
the enzyme is capable of converting useful pharmaceutical targets such as 3-oxo-DELTA4-steroids (e.g., testosterone, 11-deoxycorticosterone, androstenedione, and progesterone) mainly into their 15beta-hydroxy homologues. In addition, the enzyme hydroxylates progesterone to a minor extent at the 11alpha-, 9alpha-, and 6beta-positions
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochrome P450
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NADH
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NADH is far less efficient than NADPH
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
carbon monoxide
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cytochrome c
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ketoconazole
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Metyrapone
N-methyl maleimide
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p-chloromercuribenzoate
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
11alpha-hydroxyprogesterone
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induced by
corn steep liquor
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Isopropanol
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malt extract
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nortestosterone
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induced by
progesterone
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best inducer
sodium-meta-periodate
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tryptone
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02 - 0.203
progesterone
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.3 - 6.9
progesterone
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.4 - 201.8
progesterone
286
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0484
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cytosol
0.388
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microsomes
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 47500, SDS-PAGE
dimer
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2 components, rhizoporedoxin and rhizoporedoxin reductase, DEAE-cellulose chromatography
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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loses potency at higher temperatures
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
immobilization often results in loss of enzyme activity
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resistant to DNase
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme complex
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene CYP509C12, cloning from a cDNA library, DNA and amino acid sequence determination and analysis, phylogenetic analysis, and recombinant expression in Pichia pastoris, coexpression with NAD(P)H-dependent reductase also from Rhizopus oryzae, which improves electron transfer to CYP509C12 and thus increases the production of 11-hydroxyprogesterone by 7fold. The engineered strain displays total bioconversion of progesterone into 11alpha-hydroxyprogesterone and small amounts of 6beta-hydroxyprogesterone
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
CYP509C12 expression is induced by progesterone
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A106T/A395I
site-directed mutagenesis, the mutant shows 14.3fold higher regioselectivity for 11alpha-hydroxylation and 39.3fold increased catalytic efficiency compared to the wild-type enzyme
A106T/A395I/R409L
site-directed mutagenesis, the mutant shows 12.6fold higher regioselectivity for 11alpha-hydroxylation and 108fold increased catalytic efficiency compared to the wild-type enzyme
A106T/A395W/G379K/R409L
site-directed mutagenesis, the mutant shows higher regioselectivity for 11alpha-hydroxylation and increased catalytic efficiency compared to the wild-type enzyme
A243V/A395I
site-directed mutagenesis, the mutant shows higher regioselectivity for 11alpha-hydroxylation and increased catalytic efficiency compared to the wild-type enzyme
A243V/A395W/G397K
site-directed mutagenesis, the mutant shows higher regioselectivity for 11alpha-hydroxylation and increased catalytic efficiency compared to the wild-type enzyme
A395I
site-directed mutagenesis, the mutant shows 8.9fold higher 11alpha-hydroxylation activity compared to the wild-type enzyme
A395W/G397K
site-directed mutagenesis, the mutant shows 11.5fold higher 11alpha-hydroxylation activity compared to the wild-type enzyme
D217V/A395I
site-directed mutagenesis, the mutant shows higher regioselectivity for 11alpha-hydroxylation and increased catalytic efficiency compared to the wild-type enzyme
M155I/F165L/A395I
site-directed mutagenesis, the mutant shows higher regioselectivity for 11alpha-hydroxylation and increased catalytic efficiency compared to the wild-type enzyme
T247V/A395I
site-directed mutagenesis, the mutant shows higher regioselectivity for 11alpha-hydroxylation and increased catalytic efficiency compared to the wild-type enzyme
T247W/A395W/G379K
site-directed mutagenesis, the mutant shows higher regioselectivity for 11alpha-hydroxylation and increased catalytic efficiency compared to the wild-type enzyme
T248V/A395I
site-directed mutagenesis, the mutant shows higher regioselectivity for 11alpha-hydroxylation and increased catalytic efficiency compared to the wild-type enzyme
T89N/A106T/A395I/R409L
site-directed mutagenesis, the mutant shows higher regioselectivity for 11alpha-hydroxylation and increased catalytic efficiency compared to the wild-type enzyme
T89N/A395I
site-directed mutagenesis, the mutant shows 11.8fold higher regioselectivity for 11alpha-hydroxylation and 24.4fold increased catalytic efficiency compared to the wild-type enzyme. The production of 15beta-hydroxyprogesterone decreases from 50.4% of the wild-type to 4.8% of mutant T89N/A395I enzyme, whereas that of 11alpha-hydroxyprogesterone increases from 27.7% to 80.9%
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis