Microbial secondary metabolites Antibacterial Antifungal Antiviral activity Cytotoxic effect Interest to microbial secondary metabolites (products of microbial synthesis that are not necessary for the growth and propagation of a biological agent) is due to their unique biological properties, which are found to be practical in various industries: food, chemical, oil industry, environmental protection, agriculture, and also in the pharmaceutical industry and medicine. Such metabolites include antibiotics, exopolysaccharides, surfactants, antiviral and cytotoxic agents, enzyme inhibitors. The need to search for new products of microbial synthesis is primarily due to the rapid spread of antibiotic resistance of many pathogens of infectious diseases. In addition, studies of low-toxic antitumor compounds, immunosuppressors and enzyme inhibitors that can replace chemical analogues that exert an immunosuppressive, mutagenic and teratogenic effect on healthy human cells are important. In this paper, modern literature data on the synthesis of microbial secondary metabolites by epiphytic, free-living (including marine) bacteria (representatives of the Bacillaceae and Paenibacillaceae families), actinobacteria of the Streptomycetaceae and Micromonosporaceae families, fungi of the Trichocomaceae family (genera Talaromyces, Aspergillus, Penicillium) are given. Due to a wide range of biological activity (antibacterial, antifungal, antiviral and cytotoxic) they can be used as alternative chemical compounds in medicine, as well as in agriculture to control the quantity of phytopathogenic microorganisms.

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Tumor necrosis factor Recombinant drug (preparation) Producer Modification The paper presents data about the biological properties of the tumor necrosis factor (TNF) and drugs based on it, which are used in medical practice to combat cancer. The preparates for scientific research based on recombinant TNF have also been described. The brief information about the possibilities of obtaining TNF using unicellular pro-(Escherichia coli) and eukaryotes (Saccharomyces cerevisiae, Pichia pastoris) is given. The TNF synthesis inducers (bacterial lipopolysaccharides, phytohemaglutenin, antigens of various organisms) that are used in the cultivation of immunocompetent animals or human mononuclear cells are characterized. The possibilities of TNF modification to improve its biological properties, increase activity and reduce toxicity, create TNF nanocomposites with antibiotics, antibody fragments, and metal nanoparticles, disadvantages of the use of polyethylene glycol for modification of TNF have also been presented.

Mixture of growth substrates Increasing the efficiency of microbial technology Cultivation of microorganisms on mixture of growth substrates allows to avoid unproductive loss of carbon and energy that occurs when using monosubstrates, and also to improve efficiency of transformation of carbon substrates into biomass and to intensify synthesis of secondary metabolites. The paper analyzes the modern scientific literature of last two or five years concerning the increase of synthesis on the mixed substrates (including industrial waste) of primary (organic acids, lipids, enzymes), secondary (polyhydroxyalkanoates, polysaccharides, surface-active substances) metabolites, and also bioethanol and biohydrogen. Using mixture of substrates in microbial technologies enables to increase the rates of synthesis of practically valuable metabolites by 1.5-10 times compared with cultivation producers on corresponding monosubstrates, and in some cases even regulate the composition and properties of final product. Own experimental data on synthesis intensification on mixture of industrial waste (frying sunflower oil, waste of biodiesel production, molasses) of microbial exopolysaccharide ethapolan (producer Acinetobacter sp. IMV B-7005) and Nocardia vaccinii IMV B-7405 surfactants are presented. Unlike most scientists who empirically establish both the concentration of substrates in the mixture and the choice of monosubstrates, in our studies to increase the carbon transformation of substrates mixture into final product, the molar ratio of monosubstrate concentrations in mixture was established on the basis of theoretical calculations of the energy requirement for process biosynthesis. In addition, using mixture of waste to obtain microbial surfactants will not only reduce cost of final product, but also utilize toxic industrial waste and increase profitability of biodiesel production.

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