[Antimicrobial activity of Laetiporus sulphureus strains grown in submerged culture]. / Antimikrobnaia aktivnost' shtammov Laetiporus sulphureus v usloviiakh glubinnogo kul'tivirovaniia.

Cultural conditions for growth and fruit body formation were elaborated to four strains of Laetiporus sulphureus isolated from nature. All strains demonstrated antimicrobial activity against a wide spectrum of gram-positive and gram-negative bacteria during agar and submerged cultivation including methicillin-resistant strain of Staphylococcus aureus (MRSA) and glycopeptide-resistant strain of Leuconostoc mesenteroides. Antifungal activity was not found. The level of antimicrobial activity during submerged cultivation reached maximum after seven days of growth on specific medium with soybean meal and corn liquid; the next four weeks its increasing was not so manifested. Antimicrobial activity correlated with orange pigment secretion and cultural liquid acidification to pH 2.0-2.8 that indicates on acid nature of synthesized products.

[Effect of penicillin precursors on antibiotic biosynthesis in various strains]. / Vliianie predshestvennikov penitsillinov na biosintez antibiotika u razlichnykh shtammov.

The regularities of biosynthesis of 6-aminopenicillanic acid (6-APA), benzylpenicillin (BP) and phenoxymethylpenicillin (PMP) by the strains under the investigation did not significantly differ. In the absence of the precursor both the strains mainly synthesized 6-APA. Phenylacetic acid (PAA) and phenoxyacetic acid (POAA) provided directed biosynthesis: the fungus synthesized BP or PMP depending on the precursor nature. When the amount of the precursors was not sufficient, 6-APA was synthesized along with the penicillins. PAA proved to be a more active precursor than POAA. When both precursors were present in the fermentation broth, only BR was synthesized. An important distinction of strain 316A was its increased sensitivity to PAA especially in the initial period. After an increase in the PAA concentration the growth rate of strain 316A lowered to a greater extent than that of strain 284A. This was likely to determine the higher levels of penicillin production by strain 316A in the presence of POAA, a nontoxic precursor. A procedure for supplying the precursors was developed. Under the laboratory conditions it provided high levels of the penicillin production.

[Effect of the methods of sterilization on the quality of nutrient media and on the level of antibiotic production]. / Vliianie sposobov sterilizatsii na kachestvo pitatel'nykh sred i na uroven' obrazovaniia antibiotikov.

It was shown that conditions for heat sterilization of nutrient media for biosynthesis of antibiotics had an impact on their biochemical composition and activity of a fermentation broth in production of penicillin and erythromycin. The temperature of 120 degrees C and the time of 25 minutes proved to be optimal for sterilization of the media in regard to both preservation of their biochemical composition and providing of the maximum antibiotic productivity on the one hand and maintenance of the sterility during the fermentation process on the other hand.

[Oil and fat metabolism and the biosynthesis of penicillin]. / Metabolizm masel i zhirov v sviazi s biosintezom penitsillina.

When grown on media with vegetable oils the producer of penicillin was more sensitive to changes in the conditions of mass transfer. Their worsening resulted in a more significant decrease in the level of the mycelium productivity than that of media containing animal fats. The observed differences were associated with the fact that the rate of consumption of readily assimilated fat substrates, for instance sunflower oil, by the cells was sufficiently high even at defective aeration and agitation. Their further oxidation in the mycelium was retarded which resulted in increasing lipid levels in the cells, irreversible destruction of the mitochondria, followed by further lowering of the oxidation processes in the cells, and inhibition of basic and secondary metabolism. On media containing whale oil there were also changes in the structure of the hyphae and first of all mitochondria of Penicillium chrysogenum and inhibited oxidation of fats evident from fractional composition of the mycelium lipids. However, all these changes were less pronounced because of the low rate of the whale oil assimilation by the cells.

[Physiological role of vegetable oils during penicillin biosynthesis]. / Fiziologicheskaia rol' rastitel'nykh masel v protsesse biosinteza penitsillina.

Addition of liquid vegetable oils to nutrient media decreased the intensity of penicillin biosynthesis. The unfavourable effect of the oils was more pronounced at the beginning of the process while they were not completely utilized. Sunflower oil is a readily assimilated source of carbon. The rate of its consumption is higher than that of whale oil or lactose. Like the majority of readily oxidized sources of carbon, sunflower oil must be a repressor of beta-galactosidase and the enzymes of penicillin biosynthesis.

[Nitrogen metabolism characteristics of P. chrysogenum in relation to penicillin biosynthesis]. / Nekotorye osobennosti azotistogo metabolizma P. chrysogenum v sviazi s biosintezom penitsillina.

Quantitative correlation between the nitrogen level in the mycelium of P. chrysogenum and biosynthesis of penicillin was shown. With an increase in the nitrogen level of the mycelium, its productivity with respect to the formation of the antibiotic also increased. The high level of nitrogen in the mycelium is an obligatory but not sufficient parameter characterizing the penicillin production capacity of the mycelium. The content of acid soluble compounds in the mycelium was found to be important for estimation of its productivity. Intensively aerated mycelium contained much greater numbers of nitrogen labile forms and had higher productivity levels as compared to the mycelium grown under poor aeration.

[Characteristics of cephalosporin C biosynthesis on a synthetic medium]. / Nekotorye osobennosti biosinteza tsefalosporina C na sinteticheskoi srede.

The attitude of the cephalosporin C-producing organism to various sources of carbon and nitrogen was studied. Carbohydrates such as maltose, starch and sucrose and nitrogen sources such as mineral ((NH4)2SO4 + KNO3) and organic nitrogen (asparagine) may be successfully used for the culture growth and antibiotic biosynthesis. The use of the mineral nitrogen necessitates additional regulation of pH during the cultivation process. The effect of pH on cephalosporin C biosynthesis was studied and its optimal values were found. It was shown that methyloleate played no specific role in cephalosporin C biosynthesis. It is an additional source of carbon which may be replaced by whale oil. It was demonstrated that the 1st stage of assimilation of inorganic sulfate, i.e. its reduction was blocked in C. acrimonium 218A. The study on the problem of phases in production of cephalosporin C showed that unlike the penicillin-producing organism C. acremonium had no capacity for the antibiotic biosynthesis at the early developmental stages irrespective of the cultivation conditions.

[Physiological role of fats in the process of penicillin biosynthesis]. / Izuchenie fiziologicheskoi roli zhirov v protsesse biosinteza penitsillina.

The level of penicillin production in the presence of whale oil was shown to be higher. The stimulating effect of the oil was connected with accumulation of large biomass rather than with its specific effect on the biosynthesis. At the beginning of the process the oil eliminated the biomass accumulation lag-phase connected with beta-galactosidase repression by glucose. During the second part of the fermentation process the oil acclerated the culture growth in the presence of lactose. The rate of the oil consumption calculated for carbon was higher than that of the lactose utilization. The presence of the oil in the medium did not prevent the lactose consumption.

[Penicillium chrysogenum mycelial productivity in the 1st phase of penicillin biosynthesis]. / Izuchenie produktivnosti mitseliia Penicillium chrysogenum v pervoi faze biosinteza penitsillina.

The course of the mycelium low productivity during the first phase of the usual two-stage process of penicillin biosynthesis was studied. It was found that the low productivity of the mycelium at the beginning of the fermentation process was probably associated with catabolic regression of the penicillin-producing system. The high specific growth rate registered in the experiments (0.06-0.08 hours-1) had no negative effect on the mycelium productivity. It was not possible to connect the productivity level with the mycelium age, because young and mature mycelium had the same producitivity levels at any developmental stage under the same conditions.

[Study of the effect of microconcentrations of glucose on the biosynthesis of penicillin]. / Izuchenie vliianiia mikrokontsentratsii gliukozy na biosintez penitsillina.

A method of "acute" experiments with significant dilution of the fermentation broth is proposed for studying the effect of easily assimilable substrates on growth of the culture and production of the antibiotic by it. The effect of microconcentrations of glucose on the parameters of the process kinetics was studied with respect to penicillin. The specific effect of microconcentrations of glucose on the specific rate of the culture growth and productivity was noted.

[Abortive myxovirus infection in Ehrlich's ascitic carcinoma cells. Further study of the nature of the virus-specific structures produced by heterokaryons]. / Abortivnaia infektsiia miksovirusa v kletkakh astsitnoi kartsinomy Erlikha. Dal'neishee izuchenie prirody virusspetsificheskikh struktur, produtsiruemykh geterokarionami.

Fowl plague virus-infected cells of Ehrlich ascitic carcinoma produce a noninfectious virus which is defective in fragility of its membranes. An attempt has been made to produce nondefective virus by fusion of infected Ehrlich cells with permissive cells: infected and non-infected chicken fibroblasts. The fusion of FPV-infected and 3H-uridine labeled Ehrlich ascitic carcinoma cells with infected unlabeled chicken fibroblasts using inactivated Sendai virus resulted in production of two types of labeled virus particles: with a buoyant density in cesium chloride gradient of 1.29 g/cm3 characteristic of particles produced by infected Ehrlich cells and buoyant density 1.22 g/cm3 typical of standard influenza virus. Both types of particles has infectious activity which was greater in the virus with the density of 1.22 g/cm3. However, particles with the density of 1.22 g/cm3 are not found upon the fusion of infected Ehrlich cells with uninfected chicken fibroblasts, with chicken fibroblasts early after infection, or with chicken fibroblasts treated with actinomycin D before infection. Infected chicken fibroblasts in hybrids were shown not to use the radioactive pool of Ehrlich cells and, accordingly, the virus with the density of 1.22 g/cm3 if formed from components pre-existing in Ehrlich cells. It is suggested that the standard virus buds on the areas of membranes of permissive cells which are parts of the hybrids.

[Metabolites toxic for penicillin biosynthesis in P. chrysogenum fermentation]. / Toksichnye dlia biosinteza penitsillina metabolity v protsesse fermentatsii P. chrysogenum

Substances toxic for biosynthesis of penicillin accumulated in the medium at the end of the process during penicillin fermentation. Accumulation of such substances was associated with the mycelium autolysis. Addition of nutrient substances as soon as they are consumed prevented autolysis of the mycelium and accumulation of the toxic metabolites.

[Biosynthesis of penicillin and the biphasal development of a P. chrysogenum culture]. / Biosintez penitsillina i dvukhfaznost' razvitiia kul'tury P. chrysogenum

The two-phase pattern of penicillin biosynthesis was observed only under definite cultivation conditions. When the conditions of the culture growth changed, the productivity curve also changed. The most high productivity levels on the glucose medium and the medium with glucose and lactose were noted at the beginning and in the middle of the process respectively. Under more or less equal conditions the productivity remained at the same level.

[Carbon metabolism under conditions of regulated penicillin biosynthesis]. / Metabolizm ugleroda v usloviiakh reguliruemogo biosinteza penitsillina

Carbon metabolism of P. chrysogenum under conditions of periodical addition of the nutrients was studied. It was found that a proper rate of the carbon source addition to the culture was of significant importance for intensive biosynthesis. The use of carbon for the energetic and constructive needs was not the same at different fermentation periods.