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The data on the study of the relation between the activity of the oleandomycin biosynthesis and the operating and physical parameters of the fermenter are presented. A dependence for computation and selection of the aeration and agitation conditions of the oleandomycin biosynthesis in apparatus of different capacity is described.

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The data on the effect of the aeration and agitation conditions on biosynthesis of oleandomycin in 0.75, 3 and 50 m3 apparatus are presented. The relationship between the biosynthetic parameters, oxygen dissolution rate and specific power consumption for agitation was studied. It was shown that the values of the specific power consumption for agitation were not acceptable for scaling up the process of oleandomycin biosynthesis.

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The possibility of using different criteria for estimation of the productivity of the vegetative inoculum of the oleandomycin-producing organism was studied with a purpose of providing maximum levels of the biosynthetic process. The use of the criteria of the culture respiration intensity and accumulation of the physiologically active mycelium as the main ones was shown to be advisable. The quantity and distribution of the mycelium in samples and the time course of changes in active acidity of the medium during the inoculum growth may be used as auxiliary criteria.

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The results of the study on relation between tetracycline biosynthesis and the specific power input for agitation in pilot plant apparatus was studied. No correlation was observed between the levels of tetracycline biosynthesis and changes in the specific power input within a range of 0.6 to 2.3 kW/m3 at the expense of changes in the mixer diameter and the agitation rate, when the aeration rate was constant. It was shown that the aeration conditions were most significant for tetracycline biosynthesis. The study provided determination of the optimal aeration conditions for biosynthesis of tetracycline.

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An increase in the power input for agitation from 0.4 to 2.7 kw/m3 in oxytetracycline biosynthesis stimulated the antibiotic production due to an accelerated use of carbohydrate and nitrogen and an earlier transition of the culture to the phase of the antibiotic biosynthesis. The procedure for determination of the aeration and agitation conditions by the maximum rate of the oxygen uptake is described. The procedure is recommended for the use in the studies on determination of such conditions for the biosynthesis of of oxytetracycline in large apparatus.

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Short-term experiments on the effect of temperature on the rate of oxytetracycline biosynthesis and consumption of carbohydrates, ammonium nitrogen and inorganic phosphorus were performed under various conditions of mass exchange. Complete fermentation cycles were also carried out at the same temperatures. It was shown that the temperature optimal under conditions of a short-term experiment was not optimal for the complete fermentation cycle. In the latter case the results also depended on the aeration and agitation conditions. It is suggested that temperature has a nonspecific effect by changing the conditions of oxygen supply to the microbial culture.

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The effect of chemical foam suppressors of various classes on the intensity of Streptomyces rimosus respiration, concentrations of dissolved oxygen and carbon dioxide and gas levels in the fermentation broth of oxytetracycline was studied. Its was shown that addition of the foam suppressors, as a rule, resulted in a decreased rate of the oxygen mass transfer due to the decreased surface of the phase contact gas-liquid. This decrease was not so significant as that in case of uninhibited intensity of the fermentation broth foaming. A different character of the effect of different foam suppressors on the biosynthetic process was noted. The effect of the foam suppressors was decreased by their regular addition in low amounts.

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It was shown that intensification of cephalosporin biosynthesis is possible with the use of the inoculum grown on the seed medium enriched with the sources of carbon and organic nitrogen. The inoculum grown on the initial medium is usually added to the fermentation medium by the 31st-33rd hour of the growth, while with the use of the enriched medium it is added to the fermentation medium by the 36th-38th hour. The intensity of the culture respiration is recommended to be used as a technological parameter for estimation of the time when the inoculum may be added to the fermentation medium.

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The study on the relation between the production of gentamicin and the conditions of aeration and agitation of the fermentation broth showed the advisability of the control of these parameters with respect to the maximum rate of the oxygen uptake. Possible scaling-up of the process of gentamicin biosynthesis was shown with the use of the expression: (formula: see text).

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The results of the experiments on determination of the effect of aeration and agitation conditions on biosynthesis of tetracycline in the apparatus of semi-production capacity are discussed. It was shown that the antibiotic production level was not connected with the rate of oxygen solution expressed in the sulphite numbers, i.e. this parameter cannot be used as a scaling-up criterion. Accumulation of the antibiotic in the fermentation broth depended on the volume of the air supplied for aeration. It was determined that the level of CO2 dissolved in the fermentation broth did not reach the values having an inhibitory effect on the biosynthetic process.

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A complex of studies on the effect of technological parameters on the mass transfer coeficients with respect to O2 and CO2 was carried out. It was shown that the ratio between the mass transfer coefficients with respect to O2 and CO2 was constant and equal to 20 for the fermentation broths of the antibiotic-producing organisms studied.

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The paper presents data on the effect of CO2 dissolved in the fermentation broth on biosynthesis of tetracycline. It was shown that there was optimal concentration of CO2 for the tetracyline-producing organism. As a result of the experiments the ranges of the optimal concentrations within 2 to 8 ml of CO2 per 100 ml of the fermentation broth were determined.

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The kinetics of the biomass growth, nystatin production and carbohydrate consumption in cultures of act. noursei in 180 liter fermenters was studied. Under conditions of intensive agitation (Klas greater than 6) dependence of the specific productivity on the specific rates of growth and carbohydrate consumption was found. No such dependence between the above parameters were observed under conditions of poor agitation (Klas smaller than 3.5). It was shown that at the beginning of the cultivation process the coefficient of oxygen transfer Kla rapidly decreased. Later the value of Kla decreased slightly. Dependence of the maximum activity of the culture fluid on the average coefficient of masstransfer with respect to oxygen was observed.

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