[Effect of the producer type on the nature of antibiotic fermentation]. / Vliianie tipa produtsenta na kharakter fermentatsii antibiotikov.

Fermentation processes in production of bacitracin, a polypeptide antibiotic by Bacillus licheniformis, and oleandomycin, a macrolide antibiotic by Streptomyces antibioticus, were studied comparatively. It was shown that the antibiotic-producing actinomycete was characterized by a prolonged phase of growth retardation. The highest efficiency of the control actions was observed at the beginning of the fermentation. They were aimed at intensifying the substrate usage during the growth phase and activation of cell metabolism. Controlled cultivation of the Bacillus representative was based on its capacity of achieving the maximum growth rate possible under the certain conditions. Therefore, an increase in the quantity of the synthesized antibiotic was due, under such conditions, to inhibition of the culture growth by various means including lower mass exchange intensity.

[Effect of surface-active agents (tween-21) on indices of energy metabolism in oleandomycin producers]. / Vliianie poverkhnostno-aktivnykh veshchestv (tvina-21) na pokazateli énergeticheskogo obmena u produtsenta oleandomitsina.

The specific growth rate of Streptomyces antibioticus, a producer of oleandomycin, and the specific rate of the antibiotic accumulation in the culture medium during fermentation were investigated. On the basis of the results obtained the fermentation period was divided into 7 phases of development. The culture treated with the surfactant (Tween-21) is characterized by a higher specific growth rate during the whole fermentation and a higher specific rate of the antibiotic accumulation at the stage of the highest production as compared to the control. The ATP content, the value of the adenylate energy charge and the contents of high-molecular weight polyphosphates in the mycelium were examined. In the phase of the intensive growth St. antibioticus was characterized by a higher ATP level and a higher energy charge. More active accumulation of polyphosphates was observed in the late intensive growth phase. It was also found that after the treatment of the culture with Tween-21 it utilized polyphosphates more actively during the antibiotic biosynthesis.

[Cyclic adenosine-3',5-monophosphate in Streptomyces antibioticus and its possible role in regulating oleandomycin biosynthesis and the growth of the culture]. / Tsiklicheskaia adenozin-3',5-monofosfornaia kislota u Strptomyces antibioticus i ee vozmozhnaia rol' v reguliatsii biosinteza oleandomitsina i rosta kul'tury.

When glucose is substituted for sucrose in the fermentation medium for Streptomyces antibioticus, the pH of the cultural broth becomes more acidic, the rate of protein synthesis in the mycelium rises, and the rate of oleandomycin synthesis decreases abruptly. The dynamics of cAMP (cyclic monophosphate) accumulation was studied in the process of biosynthesis by the culture in different media. Most of the synthesized cAMP (80-90%) was shown to be excreted into the medium. Glucose stimulates cAMP synthesis and excretion from the mycelium by a factor of 1.5-3. No distinct correlation was found between cAMP content in S. antibioticus cells and the level of oleandomycin biosynthesis. A correlation between changes in the concentration of exocellular cAMP and protein synthesis in the mycelium suggests that the excreted cAMP may be involved in regulating the growth of the culture producing the antibiotic.

[Effect of carbon and nitrogen source additions on the development of a productive strain of P. nigricans Thom and on the level of adenylates in its mycelium]. / Vliianie dobavok istochnikov ugleroda i azota na razvitie produktivnogo shtamma P. nigricans Thom i uroven' adenilatov v ego mitselii.

Growth of the cultured strain og P. nigricans and dynamics of the adenylate levels in its mycelium on mineral media with 2 per cent of glucose were studied in relation to the means and time of addition of glucose, NaNO3 or their mixture to the medium. It was shown that the maximum yield of the mycelium could be obtained with addition of glucose once at the moment of inoculation. The mixture of glucose with NaNO3 provided even higher yields of the biomass but only with its fractional addition. Introduction of additional amounts of NaNO3 at the moment of inoculation and during the growth phase (5 days) inhibited the subsequent development of the culture providing stable levels of ATP and ADP, while introduction of NaNO3 on the 7th day stimulated the culture growth and the antibiotic yield. The use of NaNO3 in the mixture with glucose eliminated inhibition and increased the ratio of ATP to ADP and the antibiotic yield.

[Adenylate level in the mycelium of Penicillium nigricans Thom. grown on various carbon sources]. / Uroven' adenilatov v mitselii shtammov Penicillium nigricans Thom., vyrashchivaemykh na raznykh istochnikakh ugleroda.

Concentrations of ATP and ADP and their dynamics during cultivation (2, 5, 9 and 13 days) of a highly productive strains of P. nigricans on a mineral medium in the presence of various carbon sources, such as glucose, succinate or acetate were studied. It was shown that the levels of ATP and ADP in the mycelium depended on the carbon source: the maximum and minimum ATP concentrations were found on the glucose and acetate media respectively, the maximum and minimum ADP concentrations showed inverse dependence. The concentrations of both adenylates on the same carbon source depended on the strain. The dynamics of the adenylates levels during cultivation showed an analogous dependence on the carbon source and the strain. Thus, the highly productive strain was characterized by a constant ATP level on glucose and succinate and variation on acetate, while the ADP level was characterized by a decrease by the 9th day of cultivation on any of the carbon sources. The low productive strain was characterized by variations in the level of ATP in any media used, stability of the ADP level by the 2nd--9th day of cultivation on the glucose medium and by the 2nd--5th day of cultivation on the succinate medium and a decrease by the 9th day of cultivation on the acetate and succinate media. The ratio of ATP/ADP at the phase of griseofulvin biosynthesis (9 days) markedly increased in both the strains when cultivated on the media with any of the carbon sources.

[Effect of the cultivation temperature on the dynamics of the ATP and ADP levels and on the growth of P. nigricans Thom. Strains in the presence of various carbon sources]. / Vliianie temperatury kul'tivirovaniia na dinamiku urovnei ATF i ADF i rost shtammov P. nigricans Thom. v prisutstvii raznykh istochnikov ugleroda.

The effect of the medium high temperature (28--28.6 degrees C) on the yield of the dry mycelium and the levels of ATP and ADP in the cells of the highly and low productive strains of P. nigricans Thom, 117 and B at different developmental periods (2, 5, 9 and 13 days) on the mineral medium using glucose, succinate or acetate as the carbon sources was studied. It was shown that the effect of the high temperature depended on the strain and the carbon source. The growth stimulating effect of this factor observed in strain 117 grown on the media with the above carbon sources and strain B grown on the media with glucose and acetate as the carbon sources was evident at different periods and later replaced by suppression. The growth of strain 177 in the presence of succinate was not inhibited, while that of strain B was suppressed during the whole developmental cycle. Such an effect of high temperature on the culture growth was the result of different supply of energy in the form of ATP to the strains which was confirmed by the study of the dynamics of the levels of ATP and ADP and their ratio in the strains during the developmental process.

[Use of flour from sunflower oil cake in the biosynthesis of antigungal antibiotics]. / Ispol'zovanie muki iz shrota podsolnechnika pri biosinteze protivogribkovykh antibiotikov.

The possibility of replacing soybean meal and corn-steep liquor by food wastes of the oilpress industry and the meal of the sunflower oil cake in particular is discussed as applied to the fermentation media for production of antifungal antibiotics, such as levorin, mycoheptin, amphotericin. The studies showed that replacement of soybean meal by sunflower oil cake meal with simultaneous increasing of the amount of carbohydrates in the medium increased the levorin levels by 60--70 per cent as compared to the media used at present. When soybean meal and corn-steep liquor were simultaneously replaced by sunflower oil cake meal in amounts of 3--4 per cent the levels of mycoheptin in the fermentation broth increased by 30--65 per cent respectively. Replacement of soybean meal and corn-steep liquor by 3 per cent of sunflow oil cake meal in the medium used presently increased the amphotericin levels by 27 percent as compared to the control. Therefore, sunflower oil cake meal is a substitute of full value for soybean meal and corn-steep liquor in the fermentation media for production of antifungal antibiotics.