[Development of technology for isolation and purification of gentamicin using sorption without filtration]. / Razrabotka tekhnologii vydeleniia i ochistki gentamitsina s ispol'zovaniem metoda besfil'tratsionnoi sorbtsii.

A technology for isolation and purification of gentamicin from nonfiltered fermentation broth with the use of sorption-pulsory columns was developed as a result of the research work. The practical application of the technology will increase the yield from 30 to 57 per cent and reduce the content of the minor admixtures in the final product up to 5 per cent in comparison to the currently used process.

[Sorption of aminoglycoside antibiotics from unfiltered culture fluid]. / Sorbtsiia antibiotikov-aminoglikozidov iz nefil'trovannoi kul'tural'noi zhidkosti.

Sorption of aminoglycosides such as sisomicin, gentamicin, kanamycin and streptomycin from the non-filtrated fermentation broth by carboxylic cation exchange resins under the static conditions was studied. The optimal conditions for the sorption of the aminoglycosides and their subsequent desorption were determined (the ratio of the volumes of the sorbent and fermentation broth and the time of the sorption and desorption).

[Study of possible biological transformation of kanamycin to amikacin]. / Issledovanie vozmozhnosti biologicheskoi transformatsii kanamitsina v amikatsin.

For transformation of kanamycin A (Km) to amikacin (Ak) with acylating enzymes from B. circulans, a culture producing butirosin (Btn), cellular and acellular conversion systems and methods for chemical and biological identification of Km, Ak and Btn were developed. The level of conversion of Km to Ak in vivo and in vitro did not exceed 2 per cent.

[Selection and physiological study of culture of Bacillus circulans-- producer of butirosin]. / Selektsionnoe i fiziologicheskoe issledovanie kul'tury Bacillus circulans--produtsenta butirozina.

For isolating a highly active variant of the butirosin-producing culture, a strain forming trace amounts of the antibiotic substance was used. Exposure to nitrosomethylbiuret and nitrosoguanidine and the use of selective media containing streptomycin and butirosin resulted in a 30-fold increase in the strain productivity. Thin layer chromatography of the produced antibiotic substance in the solvent system developed by the authors, mass spectrometry and assay of the antimicrobial spectrum in regard to ++gram-positive and ++gram-negative bacteria by using the known aminoglycosidine-inactivating enzymes revealed that the substance was identical to butirosin. Along with the major product, the fermentation broth contained up to 5 per cent of ribostamycin.

[Use of mass spectrometry with chemical ionization in screening antibacterial antibiotics with a broad spectrum of action (aminoglycosides and macrolides)]. / Primenenie mass-spektrometrii s khimicheskoi ionizatsiei pri skrininge antibakterial'nykh antibiotikov s shirokim spektrom deistviia (aminoglikozidy i makrolidy).

It is shown that mass-spectrometry with ammonia desorption chemical ionization (ADCI) can be used for identification of aminoglycosides and macrolides at the initial stages of screening. ADCI can also be used for selection of strains which form the lowest amounts of by-products, as well as for optimization of biosynthetic conditions.

[Structure of the antineoplastic antibiotic variamycin]. / Stroenie protivoopukholevogo antibiotika variamitsina.

The results of the structural study of antitumor antibiotic variamycin and its peracetyl derivative by 1H-and 13C-NMR spectroscopy are reported. Structures of carbohydrate chains of the antibiotics molecule are revised. Variamycin is shown to be 2-[beta-cymmarosyl(1-3)-beta-oliosyl (1-3)-beta-olivosyl]-6-[beta-olivosyl (1-3)-beta-olivosyl] chromomycinone.

[Production of lincomycin by Micromonospora halophytica culture]. / Obrazovanie antibiotika linkomitsina ku'lturoi Micromonospora halophytica.

A Micromonospara culture designated as 991/78 with activity against gram-positive cocci and bacteria was isolated from samples of silt-covered substrates from the Amu-Darya. Directed screening on a selective medium supplemented with lincomycin in an amount of 50-100 micrograms/ml was used. Identification of the antibiotic produced by the culture showed it to be lincomycin. By its taxonomic features the culture was classified as belonging to Micromonospora (subgroup II, Cinnamomea) and in particular to M. halophytica (Weinstein, Luedemann, Oden, Wagman, 1968). Up to now, it was known that lincomycin was produced only by Streptomyces cultures.

[Study of conformation structure and molecular interactions of rosamycin by infrared spectrum analysis]. / Issledovanie konformatsionnoi struktury i molekuliarnykn vzaimodeistvii rozamitsina po IK-spektram.

IR spectra of rosamycin and its solutions in inert (CCl4 and C2Cl4), proton acceptor (tetrahydrofuran, hexametapol and diethylamine) and proton donor (CHCl3 and CH3OD) solvents were studied at various concentrations (0.1 to 0.001 mol/l) and temperatures (20 to 100 degrees C) in the region of the vC = O and vOH absorption bands (1600-1800 and 3200 3650 sm 1). It was found that the absorption bands at 3480 and 3560 sm-1 observed in the spectra of rosamycin diluted solutions in the inert solvents referred to variations of vOH...N of the aminosugar fragment and to vOH...O = C of the ester group of the macrocycle. Bands at 1697 and 1717 sm-1 referred to vC = O of the ketone and aldehyde carbonyl groups and band at 1728 sm-1 referred to vC = O of the ester group whose carbonyl was involved in the C = H...HO intramolecular hydrogen bond. Intensity of vC = O band (1745 sm-1) of the free ester group was nought. However, it increased with using the proton acceptor solvents. OH...N and OH...O = C intramolecular hydrogen bonds stabilized rosamycin molecule conformation. Mechanism of rosamycin interaction with the proton donor and acceptor molecules was elucidated. It was shown that tertiary nitrogen was the center of rosamycin molecule protonation.

[Identification of idiotrophs for 3'-deoxykanamycin B synthesis in Streptomyces tenebrarius (Higgens a. Kastner)]. / Identifikatsiia idiotrofov po sintezu 3'-dezoksikanamitsina B u Streptomyces tenebrarius (Higgens a. Kastner).

Mutants of Streptomyces tenebrarius with the blocked synthesis of 3'-deoxykanamycin B were obtained by treating the producer with NTG and chloramphenicol, or after gamma-irradiation. These mutants (idiotrophs) were distributed into three groups by means of the cosynthesis experiments on agar plates: convertors, secretors and "neutral" strains. Five idiotrophs represented five complementation groups for biosynthesis of the antibiotic. Three of these were defective in 2-deoxystreptamine synthesis, the fourth was defined as neamine-negative, and the fifth was probably blocked in regulation of enzymes responsible for conversion of neamine or paromamine into kanamycins. Localization of mutations has been shown on the scheme of kanamycins' biosynthesis.

[IR spectral research on erythromycin mono- and dihydrates]. / Issledovanie mono- i digidrata éritromitsina po IK-spektram.

The IR spectra of crystalline and amorphous forms of erythromycin monohydrate and dihydrate were investigated and their characteristic spectral features were described. Differences in the system of the intermolecular hydrogen bonds and in the level of perfection of the crystalline structures of the monohydrate and dihydrate were detected. It was shown that both crystallohydrates of erythromycin might exist in two polymorphous modifications. The crystalline structure of the low temperature modification of the monohydrate was of low perfection. At 75-80 degrees C irreversible polymorphous conversion of erythromycin monohydrate and erythromycin dihydrate accompanied by changes in the hydration water state was observed. The crystalline structures of high temperature modifications of the erythromycin crystallohydrates were identical.

[Infrared spectra and the molecular conformations of macrolide-group antibiotics in solution]. / Infrakrasnye spektry i knoformatsii molekul nekotorykh antibiotikov gruppy makrolidov v rastvore.

IR spectra (1,600-1,800, 3,100-3,700 cm-1) of tetrachlorethylene solutions of macrolide antibiotics such as erythromycin monohydrate and dihydrate, oleandomycin, erythrolose amine and anhydroerythromycin were obtained. The atoms and atomic groups included into the hydrogen bond were determined. It was shown that the antibiotic molecule conformations were stabilized by the intramolecular hydrogen bonds.

[Formation of antibiotic JI-20B by a culture of Streptomyces flavovirens]. / Obrazovanie antibiotika J120-B kul'turoi Streptomyces flavovirens.

An actinomycetous culture having an antibiotic action on gram-positive and gram-negative bacteria was isolated from a soil sample collected in the region of the Balaton Lake. As a result of the taxonomic study the culture was classified as Str. flavovirens. Waksman, Henrici (1948). Examination of antimicrobial properties of the antibiotic and chromatographic and mass-spectroscopic studies allowed one to classify it as an aminoglycoside belonging to the gentamicin group. The antibiotic was designated as J120-B. Until recently such antibiotics were known to be produced only by Micromonospora.

[Isolation of the new antibiotic variamycin B from the biosynthetic products of a Streptomyces olivovariabilis sp. nov. culture]. / Vydelenie novogo antibiotika variamitsina B iz produktov biosinteza kul'tury Streptomyces olivovariabilis sp. nov.

Variamycin B, a new antitumor antibiotic was isolated from metabolic products of Streptomyces olivovariabilis sp. nov. The empirical formula of variamycin B is C52H76O24, the melting point is 163-165 degrees C (dec.), (alpha)20D--30 +/- 2 degrees (C 0.5, alcohol), the UV-spectrum: lambda max 230, 279, 317, 330, 415 (lg E 4.27, 4.6, 3.83, 3.75, 3.95), IR-spectrum: 1080, 1170, 1380, 1570, 1640, 1720, 3400 cm-1. Variamycin B is classified as belonging to the group of antibiotic analogs of aureolic acid. Chromomycinone, tetrazide and residues of two 2,6-didesoxysugars, i.e. olivose and variose were obtained as a result of complete and partial acid degradation of variamycin B. It was shown with the data of quantitative analysis of the hydrolysates obtained on complete hydrolysis of variamycin B that the ratio between the residues of variose and olivose in the antibiotic molecule was 1 : 4. Oxidation of variamycin B with Fremi salt resulted in formation of chinone having chromomycinone-chinone, 2 residues of olivose and 1 residue of variose in its composition. Investigation of the products of partial hydrolysis provided isolation of a substance having aglicone-chromomycenone and 4 residues of olivose in its composition. A partial structure of variamycin B is proposed.

[Use of selective media with lincomycin for the directed screening of antibiotic producers]. / Ispol'zovanie selektivnykh sred s linkomitsinom dlia napravlennogo poiska produtsentov antibiotikov.

Relation between lincomycin resistance of Micromonospora cultures freshly isolated from soil samples and their capacity for production of antibiotics related to lincomycin by the structure or mode of action was shown. 32 cultures of Micromonospora were isolated from soil platings containing 50--100 microgram/ml of lincomycin. Crude antibiotic substances were recovered with the method of organic solvent extraction from 10 cultures possessing pronounced antibiotic activity. Selective inactivity (MIC more 1000 microgram/ml) of the crude substances with respect to the lincomycin resistant variant of Staph. aureus 209 p was observed, 2 of them having no inhibitory effect on the erythromycin resistant variant of the staphylococcus. The crude antibiotics inhibited the growth of the initial strain of the staphylococcus and its other antibiotic resistant variants in concentrations of 0.5--10 microgram/ml. It was demonstrated with the use of gas chromatography and mass spectrometry that one substance was lincomycin and 4 substances were known macrolides. Efficiency of the simple method of directed screening of antibiotics belonging to definite groups is indicated. Resistance of actinomycetes freshly isolated from natural substrates to various antibiotics is used as the criterion for antibiotic screening. The method provides detection of various antibiotics which are analogs in the structure or mode of action of the selecting antibiotic used for the screening.