Název: Zvýšená produkce daunomycinu u Streptomyces coeruleorub
Překlad názvu: Enhanced production of daunomycin in Streptomyces coeruleorubidus
Autoři: PUDHUVAI, Baveesh
Typ dokumentu: Disertační práce
Rok: 2024
Jazyk: cze
Abstrakt: Daunorubicin (DNR) is an anthracycline antibiotic originating from soil-dwelling actinobacteria extensively used to treat malignant tumors. Over the decades, extensive attempts were made to enhance the production of anthracyclines by introducing genetic modifications and mutations in combination with media optimisation, but the target production levels remain comparatively low. Developing an appropriate culture medium to maximise the yield of DNR and preventing auto-toxicity for the producing organism remains a challenge. Our prospective review sheds light on a method involving perturbation that enhances the precursors to regulate PKS II biosynthesis, enhancing cells' capacity to increase secondary metabolite production. The suggested method also entails the preparation of culture media for the cultivation of Streptomyces sp. and enhanced yield of DNR and making it inactive with iron or its reduced forms following efflux from the producer. The iron or iron-DNR complex is encapsulated by oleic acid or lipid micelle layers in the culture media, finally resulting in the generated inactive DNR and the DNR-iron-oil complex. This idea has the potential to protect the producer organism from autotoxicity and prevent the inhibition of metabolite production. By developing a specialized cultivation medium that integrates olive pomace oil and iron, this research successfully induces an autonomous resistance mechanism through biogenic nanoparticle formation (ADBN). The approach of substituting sugar with oil in culture media has a dual role where it promotes the Streptomyces growth by utilizing lipids as an energy source and encapsulating the generated DNR-iron complex in the medium. The amphiphilic properties of olive pomace oil not only serve as a carbon source but also facilitate the stabilization of nanoparticles, thereby enhancing the efficacy of the synthesis process due to its rich phenolic content, which promotes crucial redox reactions. The optimization of the medium composition through empirical methods resulted in a marked increase in daunomycin production, achieving yields between 5.5 and 6.0 g/L, which demonstrates a significant advancement relative to prior methodologies. This research not only contributes to the field of microbial fermentation and antibiotic production but also emphasizes the importance of minimizing environmental impacts through the production of insoluble daunomycin precipitates that can be efficiently recovered from the cultivation medium. Overall, these findings present promising avenues for further investigation into the mechanisms underlying biogenic nanoparticle formation and the optimization of cultivation processes. Such explorations may not only refine microbial production systems for daunomycin but also broaden the potential application of similar strategies for the synthesis of other therapeutically important compounds. We anticipate that our work help researchers working with secondary metabolites production and decipher a methodology that would enhance DNR yield and facilitate the extraction of the resulting DNR by lowering costs in large-scale fermentation.
Klíčová slova: autotoxicity; daunomycin; enhanced production; iron-lipid interaction; Streptomyces; autotoxicity; daunomycin; enhanced production; iron-lipid interaction; Streptomyces
Citace: PUDHUVAI, Baveesh. Zvýšená produkce daunomycinu u Streptomyces coeruleorub. České Budějovice, 2024. disertační práce (Ph.D.). JIHOČESKÁ UNIVERZITA V ČESKÝCH BUDĚJOVICÍCH. Fakulta zemědělská a technologická

Instituce: Jihočeská univerzita v Českých Budějovicích (web)
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Původní záznam: http://www.jcu.cz/vskp/60748

Trvalý odkaz NUŠL: http://www.nusl.cz/ntk/nusl-668775