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 optimization, but the target production levels remain comparatively low. Developing an appropriate culture medium to maximize the yield of DNR and preventing autotoxicity for the producing organism remains a challenge. Our prospective review sheds light on a method involving perturbation that enhances the precursors to regulate the type II PKS pathway, 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, as well as 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. The approach of substituting sugar with oil in culture media has a dual role wherein it promotes Streptomyces growth by utilizing lipids as an energy source and encapsulating the generated DNR–iron complex in the medium. In this review, we discussed aspects like anthracycline producers, biosynthesis pathways, and gene regulation; side effects of DNR; mechanisms for autotoxicity evasion; and culture media components for the enhancement of DNR production in Streptomyces sp. We anticipate that our work will 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.
30 September 2016 in Acta Ichthyologica Et Piscatoria
Honey bees coexist with fungi that colonize hive surfaces and pollen. Some of these fungi are opportunistic pathogens, but many are beneficial species that produce antimicrobial compounds for pollen conservation and the regulation of pathogen populations. In this study, we tested the in vitro antimicrobial activity of Talaromyces purpureogenus strains isolated from bee bread against Paenibacillus alvei (associated with European foulbrood disease) and three Aspergillus species that cause stonebrood disease. We found that methanol extracts of T. purpureogenus strains B18 and B195 inhibited the growth of P. alvei at a concentration of 0.39 mg/mL. Bioactivity-guided dereplication revealed that the activity of the crude extracts correlated with the presence of diketopiperazines, a siderophore, and three unknown compounds. We propose that non-pathogenic fungi such as Talaromyces spp. and their metabolites in bee bread could be an important requirement to prevent disease. Agricultural practices involving the use of fungicides can disrupt the fungal community and thus negatively affect the health of bee colonies.
Among the morphological anomalies that have been reported in fish so far, abnormalities in scale shape and structure have been described from a limited number of species worldwide. The aim of the present study was to extend this knowledge by identifying and describing such scale abnormalities in freshwater fish from the Kaniv Reservoir, Ukraine. Scale deformities were common in most of the species investigated (Cyprinidae, 10 spp.; Percidae, 2 spp.; Esocidae, 1 sp.), with some differences in the number of cases among them. A wide variety of scale deformities was found, classified into two major categories, slight and severe. In all, 211 abnormal scales (172 slight and 39 severe deformities) were observed and described. The scale deformities described herein could help direct future work on the relationships between the condition of the environment and fish health.
Daunomycin is a chemotherapeutic agent widely used for the treatment of leukemia, but its toxicity toward healthy dividing cells limits its clinical use and its production by fermentation. Herein, we describe the development of a specialized cultivation medium for daunomycin production, including a shift to oil rather than sugar as the primary carbon source. This achieved an almost threefold increase in daunomycin yields, reaching 5.5–6.0 g/L. Daunomycin produced in the oil-based medium was predominantly found in the solid sediment, whereas that produced in the sugar-based medium was mostly soluble. The oil-based medium thus induces an autonomous daunomycin-resistance mechanism involving biogenic nanoparticle formation. The characterization of the nanoparticles confirmed the incorporation of iron and daunomycin, indicating that this approach has the potential to mitigate cytotoxicity while improving yields. The presence of proteins associated with iron homeostasis and oxidative stress responses revealed the ability of the production strain to adapt to high iron concentrations. Our findings provide insight into the mechanisms of biogenic nanoparticle formation and the optimization of cultivation processes. Further investigation will help to refine microbial production systems for daunomycin and also broaden the application of similar strategies for the synthesis of other therapeutically important compounds.