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Information on EC 1.14.13.181 - 13-deoxydaunorubicin hydroxylase and Organism(s) Streptomyces peucetius and UniProt Accession Q9ZAU3

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IUBMB Comments
The enzymes from the Gram-positive bacteria Streptomyces sp. C5 and Streptomyces peucetius show broad substrate specificity for structures based on an anthracycline aglycone, but have a strong preference for 4-methoxy anthracycline intermediates (13-deoxydaunorubicin and 13-dihydrodaunorubicin) over their 4-hydroxy analogues (13-deoxycarminomycin and 13-dihydrocarminomycin), as well as a preference for substrates hydroxylated at the C-13 rather than the C-14 position.
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Streptomyces peucetius
UNIPROT: Q9ZAU3
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The taxonomic range for the selected organisms is: Streptomyces peucetius
The enzyme appears in selected viruses and cellular organisms
Synonyms
cyp109a2, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
13-deoxydaunorubicin,NADPH:oxygen oxidoreductase (13-hydroxylating)
The enzymes from the Gram-positive bacteria Streptomyces sp. C5 and Streptomyces peucetius show broad substrate specificity for structures based on an anthracycline aglycone, but have a strong preference for 4-methoxy anthracycline intermediates (13-deoxydaunorubicin and 13-dihydrodaunorubicin) over their 4-hydroxy analogues (13-deoxycarminomycin and 13-dihydrocarminomycin), as well as a preference for substrates hydroxylated at the C-13 rather than the C-14 position.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
resveratrol + NADPH + H+ + O2
piceatannol + NADP+ + H2O
show the reaction diagram
DoxA along with accessory enzymes ferrdoxin reductase and ferredoxin from spinach hydroxylates resveratrol at the 3'-position in vitro to produce piceatannol
-
-
?
daunorubicin + NADPH + H+ + O2
doxorubicin + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
daunorubicin + NADPH + H+ + O2
doxorubicin + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochrome P-450
cytochrome P-450-dependent monooxygenase
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cytochrome P450
-
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
the block in the SPDHC mutant is probably due to a defective C-13 oxidation activity of DoxA. Since this mutant accumulates 13-dihydrocarminomycin, the C-13 hydroxylation activity of DoxA is probably not affected
physiological function
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the cytochrome P450 monoxygenase DoxA is responsible for the hydroxylation of daunorubicin into doxorubicin
additional information
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protein-protein interaction and docking analysis of recombinant enzymes, structure homology modeling, DoxA active site structure, overview. Enzyme DoxA interacts with ist redox partners FDX1, FDR2, and FDX3
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DOXA_STRPE
415
0
45095
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
46096
1 * 46096, calculated from sequence
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
1 * 46096, calculated from sequence
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme DoxA from Escherichia coli, copurification with His-tagged FDX1, FDR2, FDX3, and putidaredoxin and putidaredoxin reductase from Pseudomonas putida from Escherichia coli by cobalt affinity chromatography and ultrafiltration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
doxA expression in Streptomyces peucetius
recombinant overexpression of His-tagged enzyme DoxA along with its His-tagged redox partners from Streptomyces peucetius FDX1, FDR2, and FDX3, and the putidaredoxin and putidaredoxin reductase from Pseudomonas putida, that are essential equivalents of the class I type of bacterial electron-transport system, in Escherichia coli strain BL21(DE3) harboring the GroES/EL-expressing plasmid pGro7
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lomovskaya, N.; Otten, S.L.; Doi-Katayama, Y.; Fonstein, L.; Liu, X.C.; Takatsu, T.; Inventi-Solari, A.; Filippini, S.; Torti, F.; Colombo, A.L.; Hutchinson, C.R.
Doxorubicin overproduction in Streptomyces peucetius: cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene
J. Bacteriol.
181
305-318
1999
Streptomyces peucetius (Q9ZAU3), Streptomyces peucetius ATCC 29050 (Q9ZAU3)
Manually annotated by BRENDA team
Vetrive,l K.S.; Dharmalingam, K.
Isolation and characterization of stable mutants of Streptomyces peucetius defective in daunorubicin biosynthesis
J. Genet.
80
31-38
2001
Streptomyces peucetius
Manually annotated by BRENDA team
Rimal, H.; Lee, S.; Lee, J.; Oh, T.
Understanding of real alternative redox partner of Streptomyces peucetius DoxA Prediction and validation using in silico and in vitro analyses
Arch. Biochem. Biophys.
585
64-74
2015
Streptomyces peucetius, Streptomyces peucetius ATCC 27952
Manually annotated by BRENDA team
Rimal, H.; Yu, S.C.; Lee, J.H.; Tokutaro, Y.; Oh, T.J.
Hydroxylation of resveratrol with DoxA in vitro an enzyme with the potential for the bioconversion of a bioactive stilbene
J. Microbiol. Biotechnol.
28
561-565
2018
Streptomyces peucetius (Q9ZAU3)
Manually annotated by BRENDA team