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doxA

Gene
doxA
Protein
Cytochrome P-450 monooxygenase DoxA
Organism
Streptomyces sp. (strain C5)
Length
422 amino acids
Function
Involved in the biosynthesis of the anthracyclines carminomycin and daunorubicin (daunomycin) which are aromatic polyketide antibiotics that exhibit high cytotoxicity and are widely applied in the chemotherapy of a variety of cancers. In vivo, DoxA catalyzes the C-13 hydroxylation of 13-deoxycarminomycin and 13-deoxydaunorubicin to yield 13-dihydrocarminomycin and 13-dihydrodaunorubicin, respectively, as well as the oxidation of these 13-dihydro-anthracyclines to their respective 13-keto forms, carminomycin and daunorubicin. In vitro, it also catalyzes the C-14 hydroxylation of daunorubicin to form doxorubicin (adriamycin), although this strain is not a doxorubicin producer. It is not able to accept anthracyclinones (aglycones) and anthracyclines with a 10-carbomethoxyl moiety. 13-oxidation of the anthracyclines possessing the 4-methoxy substitution is greatly favored. The anthracycline analog desacetyladriamycin can be oxidized to 10-hydroxydesacetyladriamycin. It can only use NADP. DoxA acts jointly with DauV.
Similarity
Belongs to the cytochrome P450 family.
Mass
46.096 kDa
Sequence
MSGEAPRVAVDPFSCPMMTMQRKPEVHDAFREAGPVVEVNAPAGGPAWVITDDALAREVLADPRFVKDPDLAPTAWRGVDDGLDIPVPELRPFTLIAVDGEDHRRLRRIHAPAFNPRRLAERTDRIAAIADRLLTELADSSDRSGEPAELIGGFAYHFPLLVICELLGVPVTDPAMAREAVGVLKALGLGGPQSAGGDGTDPAGDVPDTSALESLLLEAVHAARRKDTRTMTRVLYERAQAEFGSVSDDQLVYMITGLIFAGHDTTGSFLGFLLAEVLAGRLAADADGDAISRFVEEALRHHPPVPYTLWRFAATEVVIRGVRLPRGAPVLVDIEGTNTDGRHHDAPHAFHPDRPSRRRLTFGDGPHYCIGEQLAQLESRTMIGVLRSRFPQARLAVPYEELRWCRKGAQTARLTDLPVWLR

Gene
doxA
Protein
Cytochrome P-450 monooxygenase DoxA
Organism
Streptomyces peucetius
Length
415 amino acids
Function
Involved in the biosynthesis of the anthracyclines carminomycin and daunorubicin (daunomycin) which are aromatic polyketide antibiotics that exhibit high cytotoxicity and are widely applied in the chemotherapy of a variety of cancers. In vivo, DoxA catalyzes the C-13 hydroxylation of 13-deoxycarminomycin and 13-deoxydaunorubicin to yield 13-dihydrocarminomycin and 13-dihydrodaunorubicin, respectively, as well as the oxidation of these 13-dihydro-anthracyclines to their respective 13-keto forms, carminomycin and daunorubicin. In vitro, it also catalyzes the C-14 hydroxylation of daunorubicin to form doxorubicin (adriamycin), although this strain is not a doxorubicin producer. It can only use NADP. DoxA acts jointly with DnrV.
Similarity
Belongs to the cytochrome P450 family.
Mass
45.095 kDa
Sequence
MAVDPFACPMMTMQRKPEVHDAFREAGPVVEVNAPAGGPAWVITDDALAREVLADPRFVKDPDLAPAAWRGVDDGLDIPVPELRPFTLIAVDGEAHRRLRRIHAPAFNPRRLAERTDRIAAIAGRLLTELADASGRSGKPAELIGGFAYHFPLLVICELLGVPVTDPAMAREAVSVLKALGLGGPQSGGGDGTDPAGGVPDTSALESLLLEAVHSARRNDTPTMTRVLYERAQAEFGSVSDDQLVYMITGLIFAGHDTTGSFLGFLLAEVLAGRLAADADEDAVSRFVEEALRYHPPVPYTLWRFAATEVTIGGVRLPRGAPVLVDIEGTNTDGRHHDAPHAFHPDRPSWRRLTFGDGPHYCIGEQLAQLESRTMIGVLRSRFPEARLAVPYDELRWCRKGAQTARLTELPVWLR

Gene
doxA
Protein
Naphthalene 1,2-dioxygenase system, ferredoxin component
Organism
Pseudomonas sp. (strain C18)
Length
104 amino acids
Function
Component of the naphthalene dioxygenase (NDO) multicomponent enzyme system which catalyzes the incorporation of both atoms of molecular oxygen into naphthalene to form cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. Functions as an intermediate electron transfer protein via a specific interaction with iron sulfur protein components (ISP) (DoxB and DoxD).
Similarity
Belongs to the bacterial ring-hydroxylating dioxygenase ferredoxin component family.
Mass
11.446 kDa
Sequence
MTVKWIEAVALSDILEGDVLGVTVEGKELALYEVEGEIYATDNLCTHGSARMSDGYLEGREIECPLHQGRFDVCTGKALCAPVTQNIKTYPVKIENLRVMIDLS