Production of rhodomycins in Streptomyces griseoruber 4620.

The strain Streptomyces griseoruber 4620 produces, besides the anthracycline antibiotics beromycins, some other anthracyclines of the rhodomycin type. Twelve isolates exhibiting a higher antibiotic activity (up to 2.5X), as compared to the parent strain, were obtained after a spontaneous selection. The following species were isolated from the hydrolysate of mycelial extract: beta-rhodomycinone, beta-isorhodomycinone, alpha 2-rhodomycinone, epsilon-rhodomycinone and 10-deoxy-beta-rhodomycinone, which has not yet been described.

Spontaneous variability of Streptomyces glomeratus, a producer of the amthracycline antibiotics beromycins.

Spontaneous variants of the beromycin-producing strain Streptomyces glomeratus 3980 were divided into five groups (A-E) according to increasing antibiotic activity. The most active variants (group E) differed from the other types and the wild strain by a suppressed ability to produce aerial mycelium and melanoid piogment and by an increased production of propionic acid. Strains with a 12-fold higher antibiotic production capacity (with respect to strain 3980) were obtained by selection of superior segregants from submerged cultures of the E type.

Effect of cultivation conditions on the activity of the beromycin producer Streptomyces glomeratus 3980 and its spontaneous variants.

Optimal conditions for the submerged cultivation of Streptomyces glomeratus 3980, producer of the anthracycline antibiotics beromycins, and its variants were sought in media with glucose, soybean meal and salts differing in the content of ammonium sulphate. As compared with the original activity of the strain the antibiotic titre of some variants increased about 12 times on increasing the glucose concenration from 3 to 5%, or on omitting CaCO3 from the medium (i.e. under conditions leading to an increased production of propionic acid and suppression of production of the melanin-like pigment). In melanin-less variants accumulating propionate even under standard conditions the activity increased about 18-40 times in the medium with 3% glucose and 0.2% CaCO3 under conditions of more intensive aeration (i.e. under conditions when no propionic acid accumulated). Individual strains also differed in the requirement for (NH4)2SO4 in the medium, their response to changes of volume of the vegetative inoculum and semsitivity to MgSO4 x 7H2O. The biosynthetic activity of all strains was inhibited by the addition of ZnSO4 x 7H2O or CaCl2 and substitution of glucose with starch, lactose or sucrose.

[Eremomycin--a new antibiotic of the polycyclic glycopeptide group]. / Eremomitsin--novyi antibiotik gruppy politsiklicheskikh glikopeptidov.

Eremomycin is a novel antibacterial antibiotic. It was isolated at the Institute of New Antibiotics, the USSR Academy of Medical Sciences from the culture fluid of actinomycete INA-238. By its physico-chemical and biological properties the antibiotic was classified as belonging to the group of polycyclic glycopeptides. Chemical structure of eremomycin was asserted and it was shown to be a new representative of the group close by its structure to vancomycin and differing from it by the carbohydrate composition and structure of tri-phenoxytriaminotricarboxylic acid. By its anti-bacterial spectrum eremomycin was found to be close to ristomycin and vancomycin. Still, its activity was 2-10 times higher. The antibiotic was several times less toxic than vancomycin. Unlike vancomycin and ristomycin, the novel antibiotic induced no tissue necrosis after its intramuscular administration. The chemotherapeutic indices of eremomycin in treatment of staphylococcal and streptococcal sepsis in albino mice exceeded 10 times those of vancomycin. At present eremomycin is under clinical trials.

[Search for antibiotic antimetabolites]. / Izyskanie antibiotikov-antimetabolitov

Special media have been developed during the past years, which provided detection of new antibiotics with the properties of antimetabolites produced by microorganisms. Antimetabolites of amino acids, vitamins and nucleic acids were found among the antimetabolite antibiotics. The antimetabolites of nucleic acids with an antitumor activity were most interesting. This group of the compounds included 5-asacytidin and antibiotic 1719 identical to azotomycin.

[Utilization of yeast mutants with a defect in the cellular membrane in the search for anticancer antibiotics]. / Ispol'zovanie mutantov drozhzhei s defektom kletochnoi membrany pri izyskanii protivorakovykh antibiotikov

The mutants of Saccharomyces cerevisiae, strain FL 599-I B with defect cell membranes are selectively inhibited by anticancer antibiotics with different molecular mechanisms of action on DNA. At the same time they are insensitive to antibacterial antibiotics. Such mutants may be used as test-cultures in isolation of active agents with antitumor effect from complex mixtures of natural substances. The above test-object makes it easier to perform separation of antimour antibiotics from accompanying bacterial inhibitors.

[Transfer of species of the genus Actinomadura Lechevalier et Lechevalier 1970 to the genus Nocardiopsis Meyer 1976]. / O perevode nekotorykh vidov roda Actinomadura Lechevalier et Lechevalier 1970 v rod Nocardiopsis Meyer 1976.

The type cultures of four Actinomadura species (A. africana, A. coeruleofusca, A. flava, A. longispora) were studied and compared with the type culture belonging to the genus Nocardiopsis. In their morphological properties and in the composition of the cell wall, these cultures were shown to be closer to the genus Nocardiopsis Meyer 1976 rather than to the genus Actinomadura Lechevalier et Lechevalier 1970. Basing on these data, the species have been transferred to the genus Nocardiopsis.

[Intensification of the cytostatic action of adriamycin and carminomycin by amphotericin B]. / Ob usilenii tsistostaticheskogo deistviia adriamitsina i karminomitsina amfoteritsinom B.

Amphotericin B has a significant cytostatic effect on lymphadenosis cells of mice NK/LY. In a concentration of 6 units/ml it inhibits an increase in total nucleic acids by 50 per cent. Such cytostatic effect of amphotericin B combines with the effect of carminomycin and adriamycin. In concentrations having no cytostatic effect amphotericin B does not enhance the action of adriamycin and carminomycin on tumor cells.

[Role of antibiotics in the ecology of actinomycetes]. / Rol' antibiotikov v ékologii aktinomitsetov.

The organisms producing ristomycin, rifamycin, lincomycin, tobramycin, rubomycin carminomycin, olivomycin, bleomycin and actinomycin D were practically not sensitive to their own antibiotics in the concentrations close to those produced during the biosynthetic process. At the same time other actinomycetous species close to the above organisms were suppressed to a significant extent by their antibiotics in the same concentrations. The experimental data indicated that the antibiotics had a protective effect on the organisms producing them and played a significant role in ecology of the actinomycetes.

[Search for new antitumor antibiotics in the bleomycin group]. / Izyskanie novykh protivoopukholevykh antibiotikov gruppy bleomitsina.

The culture of Penicillium avellaneum 444 and its bleomycin resistant variant may serve a rather valuable specific test for detecting organisms producing new antitumor antibiotics of the bleomycin group. The organisms producing antitumor antibiotics of the group of anthracyclines (rubomycin and carminomycin), actinomycins and other chemical groups do not inhibit the growth of these test-organisms. Such tests are also resistant to the effect of antibacterial antibiotics.

[Formation of the antibiotic complex 4041 by a culture of Actinoplanes ianthinogenes subsp. octamycini subsp. nov]. / Obazovanie antibioticheskogo kompleksa 4041 kul'turoi Actinoplanes ianthinogenes subsp. octamycini subsp. nov.

A new variety of Actinoplanes, named Actinoplanes ianthinogenes subsp. octamycini Gause et Svechnikova is described. It produces an antibiotic complex consisting of purpuromycin and a new antibiotic belonging to the group of polyens, i. e. octamycin. Maximum accumulation of the above antibiotics in the mycelium was observed in the soybean-glycerol medium.

[The antibiotic varigomycin--a new representative of the carbonyl-conjugated pentaenes]. / Antibiotik varigomitsin--novyi predstavitel' karbonil-kon''iugiro-vannykh pentaenov.

In screening new antibiotics, varigomycin produced by a new fungal species Streptomyces variegatus Sveshnikova et Timuk was isolated. By physicochemical properties varigomycin belongs to carbonyl conjugated pentaens. It is a new representative of this antibiotic group. Varigomycin differs from the known representatives of this group by the presence of glucose, sugar in its molecule.

[Eremomycin--a new antibiotic from the cyclic glycopeptide group]. / Eremomitsin--novyi antibiotik iz gruppy tsiklicheskikh glikopeptidov.

Eremomycin, a novel antibiotic belonging to the group of cyclic glycopeptides is produced by an actinomycete designated INA-238. Biosynthesis, isolation, physico-chemical and biological properties of the antibiotic are described. Eremomycin is shown to be close to vancomycin. However, by its chromatographic and electrophoretic mobility, presence of chlorine in the antibiotic molecule and optic characteristics eremomycin differs from vancomycin. Eremomycin is less toxic than vancomycin whereas its chemotherapeutic activity in treatment of infections caused by gram-positive organisms is higher.

[Search for new antibiotics of the cyclosporin group]. / Izyskanie novykh antibiotikov iz gruppy tsiklosporinov.

A total of 160 fungal cultures belonging to Trichoderma were isolated from soil samples collected in various regions of the USSR. The cultures were tested for production of antibiotics of the cyclosporin group, having a narrow antifungal spectrum. It was found that 7 cultures produced substances having a selective inhibitory effect on Asp. niger and no activity against gram-positive and gram-negative organisms. An antibiotic substance close by its physicochemical properties to cyclosporins was isolated from T. viride 122.

[Formation of an antibiotic of the siomycin group by a Streptomyces corchorusii 1401 culture]. / Obrazovanie antibiotika iz gruppy siomitsina kul'turoi Streptomyces corchorusii 1401.

Streptomycete 1401 inhibiting the growth of gram-positive organisms was isolated from a soil sample in the screening of new antibiotics. By its cultural and morphological properties the culture was classified as Str. corchorusii. An antibiotic complex was isolated from the mycelium of the culture. The main component of the complex was shown to belong to the antibiotics of the siomycin group.

[Formation of the anthracycline antibiotics, beromycin and nogalamycin, by a new actinomycete species, Streptomyces glomeratus sp. nov]. / Obrazovanie antratsiklinovykh antibiotikov beromitsina i nogalamitsina novym vidom aktinomitseta Streptomyces glomeratus sp. nov.

Culture 3980 was isolated from a soil sample and described as a new species, Streptomyces glomeratus sp. nov. It was found that the culture produced simultaneously 2 close anthracycline antibiotics, i. e. nogalamycin and beromycin, which were synthesized mainly in the mycelium. S. glomeratus differed from the nogalamycin and beromycin-producing organisms described earlier.

[Formation of a new antibiotic, nocamycin, by a culture of Nocardiopsis syringae sp. nov]. / Obrazovanie novogo antibiotika nokamitsina kul'turoi Nocardiopsis syringae sp. nov.

A culture of a new actinomycetous species, Nocardiopsis syrinage was isolated from a soil sample. The antibiotic produced by it was named nocamycin. It accumulated in the culture fluid on cultivation of the organism in a nutrient medium containing soybean meal, glycerin, sodium chloride and calcium carbonate. Crystalline nocamycin had an antitumor effect. In inhibited by 72--73 per cent the development of an intraperitoneally implanted lymphadenosis of strain NK/LI in mice.

[Formation of antibiotic 2562 by a culture of the actinomycete, Streptomyces griseovariabilis]. / Obrazovanie antibiotika 2562 kul'turoi aktinomitseta Streptomyces griseovariabilis.

An actinomycetous culture 2562 inhibiting the growth of gramnegative bacteria was isolated from a soil sample. The culture was classified as Streptomyces griseovariabilis. It was found that culture 2562 produced an antibiotic belonging to the group of novobiocin. It consists of 2 components. One of them is identical to chlorobiocin and the other is a minor component of this group. Some parameters of the antibiotic complex production by strain 2562 under submerged conditions were studied. Nutrient media providing the predominant biosynthesis of the first (main) or the second component of the antibiotic were developed.

[New producer of carminomycin, Actinomycer cremeospinus sp. nov]. / Novyi produtsent karminomitsina--Actinomyces cremeospinus sp. nov.

An actinomycete strain No. 85 was isolated from a soil sample on media with bleomycin. It was described as a representative of a new species. Actinomyces cremeospinus sp. nov. An antibiotic substance identical with carminomycin, an antitumor antibiotic was isolated from the culture fluid of the strain.

[New producer of cephamycin C, Streptomyces filipinensis var. cephamycini var. nov]. / Novyi produtsent tsefamitsina C--Streptomyces filipinensis var. cephamycini var. nov

An actinomycetes strain 3016 was isolated from a soil sample on a selective medium with actinomycin as a result of directed screening of organisms producing beta-lactam antibiotics. The culture fluid of the isolate contained an antibacterial anibiotic identical to cephamycin C. Description of the strain is presented. It is a representative of new variety of streptomyces filipinensis var. cephamycini var. nov. The results of the study of the chemical properties of antibiotic 3016 and its identification with cephamycin C are also presented.