Compounds isolated at the Department of Biogenesis of Natural Substances, Institute of Microbiology, Czechoslovak Academy of Sciences, in 1984-1988.

A total of 41 compounds studied at the Department of Biogenesis of Natural Substances between 1984 and 1988 are characterized and tabulated. They include natural, semisynthetic and synthetic compounds.

Relationship between the fatty acid composition and the type of antibiotics produced by Streptomyces lasaliensis.

The GC-MS method was used to analyze fatty acids in a parent strain of Streptomyces lasaliensis and its two mutants producing only lasalocid or quinomycin. The biosynthesis of these substances bears relation to differences in the relative proportion of fatty acids. Biosynthetic relationships were revealed between the starter fatty acid units, their precursors, i.e. valine, leucine and isoleucine, and the type of the antibiotic produced.

Very-long-chain fatty acids from lower organism.

The qualitative occurrence and quantitative proportion of very-long-chain fatty acids (above C22), mainly in lower organisms and briefly in higher plants and animals is described.

Cytotoxic and mutagenic in vitro effect of 7-O-epoxyalkyl derivatives of daunomycinone. Part IX.

The cytotoxic effect of (7S)- and (7R)-O-epoxyalkyl derivatives of daunomycinone on leukemia P388 cells was followed in in vitro tests and their mutagenicity was determined by means of the bacterial SOS chromotest. The biological effects of the substances were compared with those of daunomycin, carminomycin and nogalamycin. The most efficient derivative proved to be the (7S)-9-acetyl-4-methoxy 7-O-(2,3-epoxypropyl)-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5, 12-naphthacenequinone 10 which inhibited the DNA and RNA synthesis and proliferation of P388 cells on the level of daunomycin or carminomycin. The cytotoxic and mutagenic action of 7-O-epoxyalkyl derivatives of daunomycinone was affected by the length of alkyl and its configuration.

Synthesis and biological activity of (7S)-O-epoxyalkyl derivatives of daunomycinone.

Synthesis and antibacterial activity of a number of 7-O-epoxyalkyl derivatives of daunomycinone prepared from 7-O-alkenyl derivatives of daunomycinone are described along with their inhibitory effect on leukemia P 388 cells.

Compounds isolated at the Department of Biogenesis of Natural Substances, Institute of Microbiology, Czechoslovak Academy of Sciences, in 1954-1983.

Substances studied at this department in 1954-1983 are reviewed; a total of 226 compounds are characterized in a tabular form. They include natural compounds as well as those prepared by biotransformation, by semisynthetic and synthetic methods.

Fatty acids of Streptomyces cinnamonensis, producer of monensin.

Using the gas chromatography-mass spectrometry (GC-MS) method we found in Streptomyces cinnamonensis saturated fatty acids of iso- and anteiso- types, cyclopropyl acids, and unsaturated fatty acids where the double bond position was determined by MS of their pyrrolidine derivatives.

Hydrocarbons in green and blue-green algae.

Liquid column chromatography and thin-layer chromatography were used to determine the total content of hydrocarbons and gas chromatography was used to evaluate composition of hydrocarbons in green algae (Chlorella kessleri, C. vulgaris, Chlorella sp., Scenedesmus acutus, S. acuminatus, S. obliquus) and the blue-green alga (Spirulina platensis) cultivated under autotrophic or heterotrophic conditions. In C. kessleri cultivated under heterotrophic conditions the content of hydrocarbons was found to be about 10(-2)% (per dry mass), whereas under autotrophic conditions it was about 10(-3)% (per dry mass). The highest content of hydrocarbons was detected in species of the genus Scenedesmus cultivated autotrophically (10(-1)%). Heptadecane and hexacosane were found as major alkanes, 1-heptadecene was detected among alkenes.

Isolation, characterization and biological activities of verotetrone from a mutant strain of Streptomyces aureofaciens.

A new metabolite denoted as verotetrone was isolated from the mycelium of the mutant strain Streptomyces aureofaciens NMG-2. Interpretations of physical data concerning verotetrone and its triacetate and, the determination of its degradation product indicate that verotetrone belongs to pretetramide-type metabolites. Verotetrone exhibits neither antibacterial nor antifungal activity. In vitro it inhibits the synthesis of nucleic acids as well as proteins in Ehrlich ascites carcinoma cells. Both verotetrone and its triacetate interfere in vivo with the metabolism of tumour and lymphoid cells, exhibiting antitumour or immunosuppressive activity. This activity, which is more intense with verotetrone than with its triacetate, is detectable in a dose which is already toxic in some animals.

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.

Isolation of ekatetrone, a new metabolite of producing variants of Streptomyces aureofaciens.

From a mixture of substances formed by producing strains of Streptomyces aureofaciens under conditions of submerged fermentation a new metabolite, ekatetrone, was isolated. Its isolation and basic physical and chemical data are described. Ekatetrone is a quinone derivative with a carboxamide group. In tests in vitro with cells of Ehrlich's ascites tumour evidence was provided that ekatetrone inhibits proteo- and nucleosynthesis.

The structure of ekatetrone, a metabolite of strains of Streptomyces aureofaciens.

The structure of ekatetrone has been determined from physico-chemical data obtained using the natural compound, its derivatives and products of degradation reactions. Ekatetrone was found to be the lactone of 1,8-dihydroxy-2-(1'-hydroxy-2'-carbamoyl)ethyl-9,10-anthraquinone-3-acetic acid (I). It is proposed that ekatetrone is related, biogenetically, to protetrone.

Fatty acids in green algae cultivated on a pilot-plant scale.

Fatty acids from Chlorella vulgaris, Scenedesmus obliquus var. acutus and from a mixed culture of the two strains, Melnik, were converted to methyl esters, separated by gas chromatography, and identified by means of standards. The spectrum of fatty acids included both saturated and unsaturated acids (with odd and even numbers of carbon atoms) from C12 to C22. Fatty acids C16:0, C18:0 and C20:3 were the major components in all cultures. Pure strains differed from the mixed culture in the production of C18:1, C12:0 and C19:2 acids; the first of these was present in higher amounts in pure cultures only, the latter two being found in the mixed culture. The level of lipids was lower as compared to the literature data and their extractability was affected by the manner of preparation of algae and extraction conditions.

Eurotium (Aspergillus) repens metabolites and their biological activity.

Eurotium repens mycelium cultivated under static conditions was used to isolate and identify metabolities--echinulin, physcion, erythroglaucin, flavoglaucin and asperentin; the filtrate of the culture yielded asperentin 8-methylether. The broadest biological activity spectrum was displayed by asperentin which had antibacterial and antifungal effects and, at a concentration of 86 microgram/ml, caused 50% mor7 tality in Artemia saline larvae. The highest cytotoxicity towards HeLa cells was found in physcion which caused 50% growth inhibition at a concentration of 0.1 microgram/ml.

2,2'-dimethoxy-4a,4a'-dehydrorugulosin (rugulin), a minor metabolite from Penicillium rugulosum.

A new metabolite was isolated from the culture of Penicillium rugulosum and its structure was determined from physico-chemical data. Accompanying metabolites skyrin and rugulosin were characterized by UV, IR, CD, mass and NMR spectra.

Content of fatty acids of Chlorella kessleri in a deep tank fermentation.

Chlorella kessleri cultivated in a deep tank contained 4.8% of non-polar lipid; 51% of this fraction represents saturated fatty acids, 7% unsaturated fatty acids. Our investigation of the fatty acids profile demonstrated even- and odd-numbered saturated and unsaturated fatty acids ranging from C12 to C20. Unlike in other Chlorella species, stearic acid was the dominant fatty acid found. Also shown was an elevated C16:0 fatty acid content and a reduced level of unsaturated fatty acids.