Information on EC 2.1.1.292 - carminomycin 4-O-methyltransferase

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The expected taxonomic range for this enzyme is: Streptomyces

EC NUMBER
COMMENTARY hide
2.1.1.292
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RECOMMENDED NAME
GeneOntology No.
carminomycin 4-O-methyltransferase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + carminomycin = S-adenosyl-L-homocysteine + daunorubicin
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
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Biosynthesis of type II polyketide products
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daunorubicin biosynthesis
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:carminomycin 4-O-methyltransferase
The enzymes from the Gram-positive bacteria Streptomyces sp. C5 and Streptomyces peucetius are involved in the biosynthesis of the anthracycline daunorubicin. In vitro the enzyme from Streptomyces sp. C5 also catalyses the 4-O-methylation of 13-dihydrocarminomycin, rhodomycin D and 10-carboxy-13-deoxycarminomycin [3].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + 10-carboxy-13-deoxycarminomycin
S-adenosyl-L-homocysteine + 10-carboxy-13-deoxydaunorubicin
show the reaction diagram
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-
-
-
?
S-adenosyl-L-methionine + 13-deoxycarminomycin
S-adenosyl-L-homocysteine + 13-deoxydaunorubicin
show the reaction diagram
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-
-
-
?
S-adenosyl-L-methionine + 13-dihydrocarminomycin
S-adenosyl-L-homocysteine + 13-dihydrodaunomycin
show the reaction diagram
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-
-
-
?
S-adenosyl-L-methionine + 13-dihydrocarminomycin
S-adenosyl-L-homocysteine + daunorubicinol
show the reaction diagram
S-adenosyl-L-methionine + carminomycin
S-adenosyl-L-homocysteine + daunomycin
show the reaction diagram
S-adenosyl-L-methionine + carminomycin
S-adenosyl-L-homocysteine + daunorubicin
show the reaction diagram
S-adenosyl-L-methionine + rhodomycin D
S-adenosyl-L-homocysteine + 4-O-methoxyrhodomycin D
show the reaction diagram
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?
additional information
?
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the purified enzyme does not catalyse methylation of the aglycones carminomycinone or 13-dihydrocarminomycinone
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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
S-adenosyl-L-methionine + 13-dihydrocarminomycin
S-adenosyl-L-homocysteine + daunorubicinol
show the reaction diagram
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terminal enzyme in the daunomycin biosynthesis pathway
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-
?
S-adenosyl-L-methionine + carminomycin
S-adenosyl-L-homocysteine + daunomycin
show the reaction diagram
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with the corresponding aglycones, carminomycinone and 13-dihydrocarminomycinone, as substrates, no methylated products are detected. Other 4-hydroxyanthracyclines such as aklavin and aclacinomycin A, and 4-hydroxyanthracyclinones such as erhodomycinone and aklavinone, are not substrates for the 4-O-methyltransferase. These reaction specificities indicate that glycosylation of the anthracyclinone molecule must occur before 4-O-methylation, which means that 4-O-methylation of carminomycin is probably the terminal step in the biosynthesis of daunomycin, and that daunomycinone is not an intermediate in the pathway
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?
S-adenosyl-L-methionine + carminomycin
S-adenosyl-L-homocysteine + daunorubicin
show the reaction diagram
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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no divalent cation requirement can be demonstrated for the partially purified enzyme
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
adenine
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0.25 mM, 8% inhibition
S-adenosyl-L-homocysteine
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0.025 mM, 87% inhibition
additional information
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homocysteine, adenosine, epsilon-rhodomycinone, daunomycin, and daunomycinone show little or no inhibitory activity
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001
13-dihydrocarminomycin
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pH 8.0, 37C
0.0005
carminomycin
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pH 8.0, 37C
0.025
S-adenosyl-L-methionine
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pH 8.0, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0194
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pH 8.0, 37C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8
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pH 7.5: 40% of maximal activity, pH 8.0: optimum. No pH values above pH 8.0 are evaluated due to the inherent instability of S-adenosyl-L-methionine at alkaline pH
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 45
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30C: about 90% of maximal activity, 45C: about 90% of maximal activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38713
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x * 38713, calculated from sequence
41000
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4 * 41000, SDS-PAGE
166000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 38713, calculated from sequence
tetramer
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4 * 41000, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
the crystal structure of the ternary complex of this enzyme with the bound products S-adenosyl-L-homocysteine and 4-methoxy-epsilon-rhodomycin T is determined to a 2.35 A resolution, vapor diffusion method at 20C
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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expression in Streptomyces violaceus pMK100 (epelmycin producer). The transformant produces the hybrid anthracycline antibiotic 7-O-L-rhodosaminyl-4-O-methyl-epsilon-rhodomycinone (4-O-methylepelmycin D) together with host epelmycins when cultured in antibiotic production medium in the presence of thiostrepton. Attempts on production of hybrid 4-O-methylaclarubicin and 4-O-methyl-1-deoxyobelmycin by the transformants of aclarubicin and 1-deoxyobelmycin producers are unsuccessful
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Y142W
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48% of the rate of the recombinant native enzyme with 4-methoxy-epsilon-rhodomycin T
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis
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production of a new hybrid anthracycline antibiotic. Expression in Streptomyces violaceus pMK100 (epelmycin producer). The transformant produces the hybrid anthracycline antibiotic 7-O-L-hodosaminyl-4-O-methyl-epsilon-rhodomycinone (4-O-methylepelmycin D) together with host epelmycins when cultured in antibiotic production medium in the presence of thiostrepton. Attempts on production of hybrid 4-O-methylaclarubicin and 4-O-methyl-l-deoxyobelmycin by the transformants of aclarubicin and 1-deoxyobelmycin producers are unsuccessful