ArticleJournal of bacteriology1999
Doxorubicin overproduction in Streptomyces peucetius: cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene.
Article in Journal of bacteriology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
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- Metabolic engineering of doxorubicin biosynthesis through P450-redox partner optimization and structural analysis of DoxA.Nature communications · 2026Article
- Engineering bacterial cell morphology for the design of robust cell factories.Biochemistry and biophysics reports · 2025Review
- Characterization of natural therapeutic compounds producing novel bacterial strains isolated from Hyderabad, India.Scientific reports · 2025Article
- Emerging nanocarriers designed for the enhanced delivery of doxorubicin.Nanomedicine (London, England) · 2025Review
- Isolation and Characterization of Bioactive Compounds fromMarine drugs · 2024Article
- Conjugate of Natural Bacteriochlorin with Doxorubicin for Combined Photodynamic and Chemotherapy.International journal of molecular sciences · 2024Article
- Enhancement of doxorubicin production in Streptomyces peucetius by genetic engineering and process optimization.AMB Express · 2024Article
- What is the role of microbial biotechnology and genetic engineering in medicine?MicrobiologyOpen · 2024Review
- Progress toward the Total Synthesis of Nogalamycin Using a Benzyne Cycloaddition Strategy.The Journal of organic chemistry · 2024Article
- Tomato growth stage modulates bacterial communities across different soil aggregate sizes and disease levels.ISME communications · 2023Article
- Rational Design of Daunorubicin C-14 Hydroxylase Based on the Understanding of Its Substrate-Binding Mechanism.International journal of molecular sciences · 2023Article
- Focus and Insights into the Synthetic Biology-Mediated Chassis of Economically Important Fungi for the Production of High-Value Metabolites.Microorganisms · 2023Review
- Rethinking Biosynthesis of Aclacinomycin A.Molecules (Basel, Switzerland) · 2023Review
- Recent developments in the identification and biosynthesis of antitumor drugs derived from microorganisms.Engineering microbiology · 2022Review
- An overview of the cytochrome P450 enzymes that catalyze the same-site multistep oxidation reactions in biotechnologically relevant selected actinomycete strains.Applied microbiology and biotechnology · 2021Review
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11 authors.
Funding
Abstract
Doxorubicin-overproducing strains of Streptomyces peucetius ATCC 29050 can be obtained through manipulation of the genes in the region of the doxorubicin (DXR) gene cluster that contains dpsH, the dpsG polyketide synthase gene, the putative dnrU ketoreductase gene, dnrV, and the doxA cytochrome P-450 gene. These five genes were characterized by sequence analysis, and the effects of replacing dnrU, dnrV, doxA, or dpsH with mutant alleles and of doxA overexpression on the production of the principal anthracycline metabolites of S. peucetius were studied. The exact roles of dpsH and dnrV could not be established, although dnrV is implicated in the enzymatic reactions catalyzed by DoxA, but dnrU appears to encode a ketoreductase specific for the C-13 carbonyl of daunorubicin (DNR) and DXR or their biosynthetic precursors. The highest DXR titers were obtained in a dnrX dnrU (N. Lomovskaya, Y. Doi-Katayama, S. Filippini, C. Nastro, L. Fonstein, M. Gallo, A. L. Colombo, and C. R. Hutchinson, J. Bacteriol. 180:2379-2386, 1998) double mutant and a dnrX dnrU dnrH (C. Scotti and C. R. Hutchinson, J. Bacteriol. 178:7316-7321, 1996) triple mutant. Overexpression of doxA in a doxA::aphII mutant resulted in the accumulation of DXR precursors instead of in a notable increase in DXR production. In contrast, overexpression of dnrV and doxA jointly in the dnrX dnrU double mutant or the dnrX dnrU dnrH triple mutant increased the DXR titer 36 to 86%.
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