Biosynthesis of Polyene Antibiotics and Phytohormones by Streptomyces netropsis IMV Ac-5025 under the Action of Exogenous Isopentenyladenosine

Streptomyces are active producers of a wide range of metabolites with multidirectional biological activity. Streptomyces netropsis IMV Ac-5025 synthesizes a polyene antibiotic complex in which two fractions were identified: heptaene candidine and a new tetraene fraction of unknown structure. The influence of secondary metabolites on the polyene antibiotics biosynthesis by soil streptomycetes is insufficiently explored. The aim of this work was to research the effect of exogenous isopentenyladenosine on the biosynthesis of polyene antibiotics and cytokinins by S. netropsis IMV Ac-5025. Methods. The strain was cultured in submerged cultivation condition in organic (soy) and synthetic (starch-ammonia) liquid nutrient media. The studies of biomass accumulation (gravimetric method), glucose consumption (glucose oxidase method), pH changes of culture media (ionometric method), biosynthesis of polyene antibiotics, and phytohormones (quantitative and qualitative thin layer chromatography spectrodensitometric method) were conducted. The results were analyzed in Statisticav.6.0 program. Results. It was found that polyene antibiotics are synthesized after the first day of cultivation, which indicates their role in the metabolism of streptomycetes. The biggest amount of the polyene antibiotics was accumulated in the stationary phase of producer growth (on the 7th day). It was found the decrease of polyene antibiotics and cytokinins accumulation in the producer’s biomass with the increase of exogenous cytokinin concentration from 25 ng/mL to 500 ng/mL. The bioproduction of the tetraene fraction was suppressed to a greater extent – up to 92% in the synthetic and up to 23% – in organic nutrient media. However, the amount of producer biomass increased under the action of the exogenous substance that confirming the positive effect of exogenous cytokinin on cell division of S. netropsis IMV Ac-5025. Exogenous isopentenyladenosine reduced the accumulation of endogenous cytokinins in streptomycetes biomass. Conclusions. The obtained results indicate an indirect metabolic relationship between the biosynthesis of polyene antibiotics and cytokinins in soil streptomycetes and provide a basis for the regulation of the biotechnological process for bioproduct formation with the appropriate quantitative composition of its components.

Antifungal macrocycle antibiotic amphotericin B — its present and future. Multidisciplinary perspective for the use in the medical practice

This review is devoted to a broad analysis of the results of studies of the effect of macrocyclic antifungal polyene antibiotic amphotericin B on cell membranes. A multi-prolonged study of polyenes showed that some of them can have not only antifungal, but also antiviral and antitumor action. Fungal pathology develops especially quickly and in this case leads to invasive aspergillosis, which contributes to the complication of coronavirus infection in the lungs and even secondary infection with invasive aspergillosis in the context of a global pandemic. The treatment of an invasive form of bronchopulmonary aspergillosis is directly related to the immunomodulatory and immunostimulating properties of the macrocyclic polyene drug amphotericin B. The article presents experimental data on the study of the biological activity and membrane properties of amphotericin B and the effect of its chemically modified derivatives, as well as liposomal forms of amphotericin B on viral, bacterial and fungal infections. The mechanism of action of amphotericin B and its analogues is based on their interaction with cellular and lipid membranes, by forming ion channels of molecular size in them. The importance of these studies is that polyenes are sensitive to membranes that contain sterols of a certain structure. The analysis showed that pathogenic fungal cells containing ergosterol were 10-100 times more sensitive to polyene antibiotics than host cell membranes containing cholesterol. The high sterol selectivity of the action of polyenes opens up broad prospects for the use of polyene antifungal drugs in practical medicine and pharmacology in the treatment of invasive mycoses and the prevention of atherosclerosis. In this connection, it should be noted that polyene antibiotics are the main tool in the study of the biochemical mechanism of changes in the permeability of cell membranes for energy-dependent substrates. Chemical and genetic engineering transformation of the structure of polyene antibiotic molecules opens up prospects for the identification and creation of new biologically active forms of the antibiotic that have a high selectivity of action in the treatment of pathogenic infections.

Isolation and biological evaluation of roseofungin and its cyclodextrin inclusion complexes

Roseofungin belongs to polyene antibiotics which is more active and less toxic comparing other polyenes of this group. Roseofungin was isolated from Actinomyces roseoflavus var. Roseofungini using different chro-matographic techniques and for the first time, the complexation of roseofungin with α-, β- and γ-cyclodextrin derivatives was performed. The binding patterns of the resulted complexes were studied in silico using mo-lecular docking techniques. The best binding mode was for roseofungin against γ-CD with an affinity value of ˗42.98 kcal/mol. The proposed binding mode of roseofungin against α-CD showed unusual interaction with an affinity value of ˗41.80 kcal/mol. Also, roseofungin bonded to β-CD with a binding affinity value of ˗35.03 kcal/mol. The antiradical and cytotoxic activities of roseofungin and its obtained α-, β- and γ-cyclo-dextrin complexes were determined. The antiradical activity was performed using butylhydroxyanisole as a reference, while the cytotoxic activity was determined using Artemia salina crustaceans. As a result of the biological activity study, it was found that roseofungin and some of its complexes have weak antiradical activities.

Inhibiting Effect of Macrolide Polyene Antibiotics on Reproduction of Viruses

The review provides a comparative analysis of the inhibitory effect of macrocyclic polyene antibiotics on the reproductive properties of some viruses of various structures — vesicular stomatitis virus (VSV), human immunodeficiency virus (HIV), enterovirus, influenza virus, etc. The data on the morphological structure of viruses and on the mechanism of penetration of viruses into cells are presented. The article also provides data on the transcription, assembly of viruses, and inhibition of the process of virus replication in cell cultures in vitro using macrolide polyene antibiotics. On the basis of experimental data for the studied viruses, a polyene antibiotics' blocking mechanism of the process of virus penetration through cytoplasmic membranes and their reproduction in the cell is proposed.