In vivo and in vitro bioconversion of epsilon-rhodomycinone glycoside to doxorubicin: functions of DauP, DauK, and DoxA
| Autor: | William R. Strohl, M L Dickens, Nigel D. Priestley |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Daunorubicin
Recombinant Fusion Proteins Restriction Mapping Hydroxylation Microbiology Streptomyces Substrate Specificity Gene product chemistry.chemical_compound Bacterial Proteins Cytochrome P-450 Enzyme System Biosynthesis medicine Anthracyclines Doxorubicin Molecular Biology chemistry.chemical_classification Strain (chemistry) biology Carubicin Esterases Glycoside Methyltransferases biology.organism_classification Models Chemical chemistry Biochemistry Genes Bacterial Multigene Family Research Article medicine.drug |
| Zdroj: | Journal of Bacteriology. 179:2641-2650 |
| ISSN: | 1098-5530 0021-9193 |
| DOI: | 10.1128/jb.179.8.2641-2650.1997 |
| Popis: | We recently determined the function of the gene product of Streptomyces sp. strain C5 doxA, a cytochrome P-450-like protein, to be daunorubicin C-14 hydroxylase (M. L. Dickens and W. R. Strohl, J. Bacteriol. 178: 3389-3395, 1996). In the present study, we show that DoxA also catalyzes the hydroxylation of 13-deoxycarminomycin and 13-deoxydaunorubicin to 13-dihydrocarminomycin and 13-dihydrodaunorubicin, respectively, as well as oxidizing the 13-dihydro-anthracyclines to their respective 13-keto forms. The Streptomyces sp. strain C5 dauP gene product also was shown unequivocally to remove the carbomethoxy group of the epsilon-rhodomycinone-glycoside (rhodomycin D) to form 10-carboxy-13-deoxycarminomycin. Additionally, Streptomyces sp. strain C5 DauK was found to methylate the anthracyclines rhodomycin D, 10-carboxy-13-deoxycarminomycin, and 13-deoxy-carminomycin, at the 4-hydroxyl position, indicating a broader substrate specificity than was previously known. The products of Streptomyces sp. strain C5 doxA, dauK, and dauP were sufficient and necessary to confer on Streptomyces lividans TK24 the ability to convert rhodomycin D, the first glycoside in daunorubicin and doxorubicin biosynthesis, to doxorubicin. |
| Databáze: | OpenAIRE |
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