Protein
Cytochrome P-450 monooxygenase DoxA
Organism
Streptomyces sp. (strain C5)
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.
Sequence
MSGEAPRVAVDPFSCPMMTMQRKPEVHDAFREAGPVVEVNAPAGGPAWVITDDALAREVLADPRFVKDPDLAPTAWRGVDDGLDIPVPELRPFTLIAVDGEDHRRLRRIHAPAFNPRRLAERTDRIAAIADRLLTELADSSDRSGEPAELIGGFAYHFPLLVICELLGVPVTDPAMAREAVGVLKALGLGGPQSAGGDGTDPAGDVPDTSALESLLLEAVHAARRKDTRTMTRVLYERAQAEFGSVSDDQLVYMITGLIFAGHDTTGSFLGFLLAEVLAGRLAADADGDAISRFVEEALRHHPPVPYTLWRFAATEVVIRGVRLPRGAPVLVDIEGTNTDGRHHDAPHAFHPDRPSRRRLTFGDGPHYCIGEQLAQLESRTMIGVLRSRFPQARLAVPYEELRWCRKGAQTARLTDLPVWLR