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. 13-deoxydaunorubicin + H(+) + NADPH + O2 = 13-dihydrodaunorubicin + H2O + NADP(+) 13-dihydrodaunorubicin + H(+) + NADPH + O2 = daunorubicin + 2 H2O + NADP(+) 13-deoxycarminomycin + H(+) + NADPH + O2 = 13-dihydrocarminomycin + H2O + NADP(+) 13-dihydrocarminomycin + H(+) + NADPH + O2 = carminomycin + 2 H2O + NADP(+) Strongly inhibited by dithiothreitol and high ionic strength buffers. kcat is 0.63 sec(-1) for oxidation on 13-dihydrodaunorubicin. kcat is 0.024 sec(-1) for hydroxylation on 13-deoxydaunorubicin. kcat is 0.00026 sec(-1) for oxidation on 13-dihydrocarminomycin. kcat is 0.00012 sec(-1) for hydroxylation on daunorubicin. Optimum pH is 7.5. This optimal pH, slightly higher than normal physiological conditions, may be necessary to ensure that the proper ionic nature of the zwitterionic anthracycline substrates is maintained for optimal recognition. Optimum temperature is 30 degrees Celsius. Antibiotic biosynthesis; daunorubicin biosynthesis. Antibiotic biosynthesis; carminomycin biosynthesis. Monomer. Streptomyces sp. C5 produces significant quantities of doxorubicin only when doxA is strongly overexpressed, but under normal conditions, 14-hydroxylation of daunorubicin cannot favorably compete with baumycin biosynthesis from daunorubicin. S.peucetius subsp. caesius ATCC 27952, a mutant strain derived from S.peucetius ATCC 29050, is the only organism reported to produce doxorubicin in vivo (PubMed:9864343). Belongs to the cytochrome P450 family.