Dependence of erythromycin biosynthesis on the active acidity of the medium]

Dependence of erythromycin biosynthesis on the medium active acidity was studied by the following methods: by changing pH of the initial medium, by changing the concentration of the medium components determining the active acidity of the culture, by using buffer mixtures by automatic control of pH. It was found that pH of the initial medium within 5.7-8.1 had no effect on the culture growth. Biosynthesis of erythromycin markedly decreased at pH 6.3 or lower. The values of pH within 6.6-7.5 (optimal values 6.7-6.9) were favourable for the antibiotic biosynthesis. At pH 6.2-6.3 the antibiotic accumulation was equal to 5-10 per cent of the control.     

Effect of several components of the nutrient medium on the biosynthesis of tobramycin

The optimal concentrations of mineral phosphorus for the growth of the tobramycin-producing organism and for the production of the antibiotic by it in the synthetic medium were determined. Introduction of an additional source of mineral phosphorus into the rich soybean medium resulted in decreased levels of antibiotic production. The stimulating effect of manganese sulfate on the biosynthesis of tobramycin in the rich medium was shown. The stimulating effect of soybean, linseed and palm oils on the production of tobramycin was evident when the fermentation period was longer.     

Study of the dynamics of n-propyl alcohol in an Act. erythreus culture during the biosynthesis of erythromycin using a gas-liquid chromatographic method]

The effect of n-propyl alcohol on biosynthesis of erythromycin and the dynamics of the precursor consumption were studied with the method of gas-liquid chromatography. It was shown that neither the optimal concentration of the precursor, nor its stimulating effect on different media correlated. n-Propyl alcohol was used not only for the antibiotic biosynthesis but also according to other metabolic path-ways and in addition its evaporation from the medium was registered. During the first period of the fermentation n-propyl alcohol suppressed the antibiotic biosynthesis.     

Biosynthesis of the non-polyene antibiotic imbricin in the medium containing the producer culture filtrate]

Imbricin (macrolide nonpolyen antibiotic) biosynthesis conditions was investigated in the medium containing culture filtrate of its producer--Streptomyces imbricatus. It was demonstrated that filtrate contains some regulator substance affecting the antibiotic biosynthesis and metabolism processes of actinomycetes S. imbricatus. Maximum of regulator accumulation coincides with maximum of antibiotic biosynthesis, and amount of synthesized imbricin is proportional to the amount of the culture filtrate added to the medium. When low active mutant of S. imbricatus was grown in the medium with added regulator its activity achieved the control level. It was shown that stimulating activity of the producer's culture filtrate is not connected with pH changes or with supplement with some additional nutritional substrates.     

Effect of inorganic phosphorus on the biosynthesis of polymyxin B]

A synthetic medium containing optimal levels of the sources of carbon, nitrogen and inorganic phosphorus and providing satisfactory yields of polymyxin B was developed for 2 strains of Bac. polymyxa 933 and VK-153. The consumption of phosphorus in the medium by the strains and the antibiotic biosynthesis levels depended on the form of phosphorus added to the medium. Optimal biosynthesis of polymyxin B was observed at lower concentration levels of soluble soluble phosphorus in the medium than the bacterial growth.     

The role of succinic acid in the biosynthesis of levorin

The influence of succinic acid as a component of media for biosynthesis of levorin, a polyenic antibiotic was studied. It was shown that with the use of the soybean-corn medium supplemented with succinic acid (0.05-0.4 per cent) the antibiotic content in the fermentation broth was higher than that in the control. The highest stimulating effect (135 per cent) was observed with addition of 0.1 per cent of succinic acid. For providing optimal antibiotic production in the synthetic medium supplemented with succinic acid (0.4 per cent) addition of acetic acid (0.05 per cent) was required. Studies with the soybean-corn medium with and without succinic acid revealed differences in the level of p-aminoacetophenone, an aromatic fragment of the levorin molecule. Under the conditions of the medium with succinic acid the content of p-aminoacetophenone in the mycelium was higher by 10 to 18 per cent as compared to that in the control and depended on the fermentation period. The role of succinic acid in biosynthesis of levorin is discussed.     

Effects of nutrients on the production of AK-111-81 macrolide antibiotic by Streptomyces hygroscopicus

The influence of different carbon and nitrogen sources on the production of AK-111-81 nonpolyenic macrolide antibiotic by Streptomyces hygroscopicus 111-81 was studied. Substitution of glucose with lactose or glycerol significantly affected maximal antibiotic AK-111-81 productivity as the growth rate was close to that of the basal fermentation medium. Addition of ammonium succinate to the fermentation medium markedly increased the antibiotic productivity as the growth rate was low. Divalent ions as Mn2+, Cu2+, Fe2+ stimulated AK-111-81 antibiotic biosynthesis. These results allow us to develop a new fermentation medium showing 6-fold increase of AK-111-81 antibiotic formation compared with the basal fermentation medium.     

Influence of the culture medium on the production of iturin A by Bacillus subtilis

The production of iturin A by Bacillus subtilis was studied with respect to the composition of the culture medium. Increasing phosphate concentrations did not modify the antibiotic yield. Fructose, sucrose and mannitol were better carbon sources than glucose for antibiotic production. The nature of the nitrogen source was an important factor in the production of antibiotic. Among the amino acids which are components of iturin A, L-asparagine was the best substrate for the biosynthesis of iturin A; L-glutamine and L-serine were rather poor substrates while L-proline and D-tyrosine gave no antibiotic. Ammonium salts permitted good synthesis of antibiotic but the addition of calcium ions to the culture medium inhibited the excretion of antibiotic from the cells.     

Effect of polyploidogenic factors on Trichothecium roseum mycelium in the process of trichothecine and fibrinolytic enzyme biosynthesis

The effect of colchicine and boric acid on the substrate mycelium of Trichothecium roseum was studied in the course of trichothecin biosynthesis. Addition of boric aicd (0.01%) and colchicine (0.1%) to the medium for biosynthesis increased the antibiotic activity of the fungus, this being due to the specific effect of polyploidogenous factors on growth of the mycelium and the proportion of nuclei in it. The number of nuclei increased in cells of the substrate mycelium correlating with a higher antibiotic activity.     

Effect of the seeding culture media on the biosynthesis of eremomycin

Relationship of eremomycin biosynthesis to the quantity and quality of the inoculate (age, aeration rate, number of subcultures) was studied. The seed medium composition for cultivating the inoculate was defined. A procedure for cultivation of the seed material for biosynthesis of eremomycin providing an increase in the antibiotic yield by 24 per cent was developed.     

Optimisation of synthetic medium composition for levorin biosynthesis by Streptomyces levoris 99/23 and investigation of its accumulation dynamics using mathematical modelling methods

The composition of a synthetic culture medium for levorin biosynthesis by Streptomyces levoris 99/23 was optimised using mathematical modelling methods. The optimal concentrations of the medium components were established by means of an optimum composition design at three factor variation levels. An adequate regression model was obtained. Levorin biosynthesis by Streptomyces levoris 99/23 in the optimised synthetic medium was over 38% higher than in the initial medium. The antibiotic biosynthesis dynamics in the optimised culture medium was studied by means of a non-linear differential equation system. The resultant model was valid.     

Effect of glycerin on the biosynthesis of heliomycin by Streptomyces olivocinereus

Glycerol as the sole carbon source was added to the medium or biosynthesis of heliomycin by Streptomyces olivocinereus and the effect of its concentration on the culture growth and antibiotic production was studied. The culture growth and the amount of the antibiotic synthesized per 1 unit of the fermentation broth were limited by glycerol added in quantities of 0.05 to 1 per cent. Further increasing of the glycerol concentration had no significant effect on the culture growth and antibiotic biosynthesis. The amount of the antibiotic synthesized per 1 unit of the mycelial mass relatively slightly depended on the glycerol concentration. The rate of glycerol consumption by the young 24-hour culture in batch fermentations markedly exceeded that of glycerol consumption by the 48-hour culture. The younger mycelium significantly increased its rate of glycerol consumption when the initial concentration was increased whereas the rate of glycerol consumption by the more mature mycelium did not depend on the initial concentration of the carbon source (within 0.5-2 per cent). The rate of heliomycin biosynthesis practically slightly depended on the initial concentration of glycerol.     

Effect of the culture medium composition on bacitracin synthesis and sporulation in Bacillus lichenformis 28 KA

The effect of the culture medium composition on the bacitracin synthesis and sporulation in Bacillus licheniformis 28 KA was being studied. During the producer's growth on a medium with tripton a biphasic pattern of the process was observed, i.e. a rapid growth of the bacterial biomass was accompanied by the production of insignificant amounts of the antibiotic. The maximum efficiency of the antibiotic synthesis coincides with the end of the exponential growth phase and the onset of sporification. The efficiency of sporification amounts up to 95% when the above mentioned medium is used. The substitution of glutamate for trypton results in a dramatic deceleration of the bacterial growth and biomass accumulation, and the process of the antibiotic biosynthesis ceases to be biphasic, i. e. the antibiotic is synthesized during the trophophase. Under the conditions when the antibiotic production drops to zero by the middle of the exponential growth phase, sporulation is virtually suppressed.     

Biosynthesis of Cobalamine,Erythromycin and Chlortetracycline by Streptomyces Species

Attempts were devoted to use Streptomyces aureofaciens and Streptomyces erythreus, the antibiotics producers as sources for the biosynthesis of cobalamine. The constituents of the fermentation medium and the strain play an important role in the biosynthesis of vitamin B₁₂. The same strain produced different amounts of antibiotic and vitamin on the two different constitutive media. The increase of the phosphorus concentration in the fermentation medium—within limits—increased the vitamin B₁₂ biosynthesis. The optimal concentration of phosphorus favourable for the synthesis of cobalamine was inhibitive for the antibiotic production. The phosphorus level in the fermentation medium plays an important role in the metabolism of carbohydrate and consequently on the biosynthesis of antibiotics. Low concentration of 5,6-dimethylbenzimidazole (cobalamine precursor) in the presence of suitable phosphorus induced the microorganism to increase its biosynthetic potentiality for the vitamin B₁₂ production.     

Influence of the composition of the medium and the duration of cultivation on the growth of Actinomyces spheroides and their biosynthesis of intracellular proteases and novobiocin

The growth of Actinomyces spheroides 35 under different conditions and the biosynthesis of biomass, proteases and the antibiotic were studied with two types of growth medium: a control one and an optimized one. The rate of biomass accumulation was by 5--7 per cent higher on the latter medium than on the former one. The dynamics of accumulation was studied with novobiocin and proteases which hydrolyzed fibrin and casein. Fibrin hydrolyzing proteases were found to be synthesized under conditions that were unfavourable for the production of novobiocin. If the production of the antibiotic was supressed, the concentration of fibrinolytic proteases in the cultural broth increased almost proportionally. Such a relation has not been found for caseinolytic proteases.     

Nutritional requirements ofLysobacter lactamgenus for the production of cephabacins

Summary To optimize the fermentation medium for the production of new cephem compounds, cephabacins, by an eubacteriaLysobacter lactamgenus IFO 14,288, the effects of medium components on cephabacin production were investigated. Supplementation of glucose as a sole carbon source in liquid media was the best for the antibiotic production as well as for the cell growth. Casamino acid was the best nitrogen source for antibiotic biosynthesis and cell growth among nitrogen sources tested, and this strain could utilize sulfate or thiosulfate as a sulfur source. No significant effects of growth factors (vitamins) on the antibiotic production and cell growth were observed, but ferrous, magnesium and nickel ions slightly enhanced the cephabacin production.     

林肯链霉菌合成林可霉素代谢调节的研究

在摇瓶条件下研究了葡萄糖、铵盐、磷酸盐对林可霉素产生菌林肯链霉菌的生长及林可霉素生物合成的影响。发酵过程中林可霉素的合成主要发生在菌体生长期,逐渐下降。使用6%的葡萄糖未发现通常所说的“葡萄糖效应”。0.2%铵盐有利于细胞生长,但0.8%NH+4对林可霉素的生物合成具有抑制作用。发酵48h后补加0.6% NH^＋_４,对林可霉素的生成没有显著影响。0.05%～0.1%磷酸盐对林可霉素合成具有较强的抑制作用。并就磷酸盐对菌体由初级代谢转向次级代谢的作用作了初步考察。     

Reproducibility of the biosynthetic parameters in various fermentation equipment

The final parameters of tetracycline biosynthesis in different fermentation apparatus were analysed comparatively with an account of possible changing of the fermentation broth volume against the initial one due to water evaporation. It was shown that for comparison of the biosynthesis parameters in different fermentation apparatus it is necessary to reestimate the activity values or the antibiotic concentration in a unit of the medium volume with respect to the initial volume of the fermentation medium charged into the apparatus.     

Some characteristics of fucidin biosynthesis]

Some features of fusidin biosynthesis by 2 strains of Fusidium coccineum were studied proceeding from the peculiar properties of the antibiotic molecule structure. It was found that an increase in the levels of the carbon sources in the medium stimulated the biosynthesis of fusidin, while excessive concentrations of nitrogen especially in its inorganic and amino acidpeptide forms stimulated the organism growth and lowered the antibiotic activity levels. The concentration of nitrogen in the medium is considered as one of the possible control mechanisms in the processes of the fungus growth and biosynthesis of fusidin.     

Effect of culture parameters on tobramycin biosynthesis

The effect of temperature, aeration and active acidity of the medium on biosynthesis of tobramycin was studied. The optimal temperature conditions (37 degrees C) were developed. It was shown that biosynthesis of tobramycin depended on the aeration conditions, especially at the beginning of the fermentation process. The initial pH 4.9-6.35 and 6.35-7.1 were found to be optimal for the growth of the tobramycin-producing organism and biosynthesis of the antibiotic, respectively.