Ampullosporin (I; Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leuol) was isolated from the mycelium of Sepedonium ampullosporum as a new 15-membered peptaibol-type antibiotic. The structure was determined by mass spectrometric and two-dimensional NMR experiments. Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phomadestructive causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg.Microbial metabolites inducing the morphogenesis and cytodifferentiation of other microbes have been shown to display interesting pharmacological activities1}. Recently we described a fungal strain, Phomadestructive which responded during surface cultivation to small amounts of cyclosporin A by the formation of a blackish pigment2). In a screening for similar inducers of pigment formation we discovered the chrysospermins2'3) as new peptaibol-type antibiotics4) from Apiocrea chrysosperma which showed the same effect as this immunomodulatory compound. But several other peptaibols such as alamethicin4) and bergofungin5) failed to afford this phenomenon.In order to obtain moreinformation about structureactivity relationships of the peptaibol antibiotics as inducers of pigment formation, we searched for other peptides from fungal cultures that could affect Phoma destructiva. Here, we report on a newpeptaibol-type antibiotic, ampullosporin (I) from Sepedonium ampullosporum HKI-0053, which is active in the same manner as described for cyclosporin A and chrysospermins2). Moreover, ampullosporin was found to induce hypothermia in mice suggesting a neuroleptic activity. Materials and MethodsMicroorganism and Cultivation Sepedonium ampullosporutn HKI-0053 was obtained from the culture collection of the Hans-Knoll-Institute of Natural Product Research Jena (Germany). The strain SEPT. 1997 was deposited in the DSMZculture collection (Braunschweig, Germany) under the registry number DSM 10602. Fifteen days agar-plate cultures (25°C) were prepared as seed mediumcomposed of malt extract 4%, yeast extract 0.4%, agar 1.5% and deionized water, pH 6.0. Four to five cm2 areas of the agar-plate cultures were used to inoculate a liquid mediumcomposed of glycerol 3%, glucose 1%, peptone 0.5%, NaCl 0.2%, molecular sieve (0.5nm, Merck) 0.1% and agar 0.1%, pH 7.0. The surface cultivation was carried out at 25°C in 1 liter Erlenmeyer flasks containing 100ml of the above medium for two weeks. Subsequently, the whole culture broth was extracted twice with two volumes of ethyl acetate.Instruments and Analytical Methods HPLCwas carried out using a Gilson binary gradient HPLCsystem equipped with a UV detector (210nm). Positive ion FABmass spectra were recorded on an AMD402 double-focussing mass-spectrometer with BE geometry (AMD, Intectra, Harpstedt, Germany). Ions were produced by Cs+ ion bombardment generated by a Cs+ gun (liquid SIMSsystem, AMDIntectra). Peptide solutions were mixed with 3-nitrobenzyl alcohol as matrix on the FABprobe tip. High-resolution...

Aurantimycins A (1), B (2) and C (3) were isolated from the mycelium of Streptomyces aurantiacus JA 4570 as new representatives of the azinothricin group of hexadepsipeptide antibiotics. Their structures were settled by X-ray diffraction analysis of crystalline aurantimycin A (1), high field homo-and heteronuclear 2D NMRexperiments, high-resolution mass spectrometry and amino acid analysis. Aurantimycins are characterized by a newside chain containing fourteen carbon atoms. They display strong activity against Gram-positive bacteria and cytotoxic effects against L-929 mouse fibroblast cells.

Four new membersofpeptaibol antibiotics, designated as chrysospermins A, B, C, and D, were isolated from the mycelium of Apiocrea chrysosperma AplOl by solvent extraction, silica gel chromatographyand preparative recycling HPLC. Their structures as newnonadecapeptides were settled by detailed spectroscopic analysis and chemical degradation experiments. The chrysospermins display antibacterial and antifungal activity, and induce pigment formation by the fungus Phoma destructiva.

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~ ~~From the intact cells of the sulfur-metabolizing hyperthermophilic archea Thermococcus tadjuricus (strain Ob9) and Thermococcus acidaminovorans (strain Vc6bk) 23 predominantly new cyclic polysulfides could be isolated by using chemical screening methods. The structures of nine preparatively separated compounds were determined by spectroscopic methods, whereas those of 14 compounds were established by GC-MS only. Most of the polysulfides are derivatives of 1,2,4-trithiolane, 1,2,4,5-tetrathiane and 1,2,3,5,6-pentathiepane. They differ from each other by aliphatic or aromatic side chains, derived from predominantly metabolized proteinogenic amino acids. The building mechanism and the relevance of the polysulfides are discussed.In 1977 the prokaryotic archaea were established as the "third domain of life" besides eukaryotes and bacteria by WoeseL21. They grow under extreme conditions like absence of oxygen, temperatures of 100°C and saturated salt solutions reminding of the primitive earth. Therefore, the name "archaea" was chosen. Due to their outstanding phylogenetic position and the resistance of their cell components to heat or salt, they are of special interest in science and technol~gy[~I. So far, very few investigations have been made. In this paper the characteristics of various hyperthermophilic archaea in our chemical screening are rep~rted[~.~]. We found several lipophilic compounds in sulfur-metabolizing strains of the genus Thermococcus. From the culture broth of 7: celer (strain Mb2) the known antifungal cyclic polysulfide lenthionin (1,2,3,5,6-~entathiepane, 14)[6,71 could be isolated besides the amino acid catabolites phenylacetic acid, p-hydroxyphenylacetic acid and indoleacetic acid [*]. From the intact cells of 7: tadjuricus (strain Ob9) and 7: uciduminovorans (strain Vc6bk) a large number of related cyclic polysulfides were obtained. The isolation and structure elucidation of most of these components as well as the synthesis and the biological activity of some of them are described in this paper. Isolation and Structure ElucidationThe strains Ob9 and Vc6bk were isolated from marine hydrothermal systems near Obock (Djibouti) of both strains on silica gel TLC plates attracted our attention due to a great number of spots, which were detectable after staining with palladium(I1) chloride. Cultivation of the strains was carried out under nitrogen in 300-1 fermenters at 85°C in a medium containing yeast extract (0.2%), peptone (0.2%) and sulfur (0.2%). After 17 hours the culture broth was cooled to 4°C and centrifuged; the cells were homogenized in acetone to yield 4 g of a malodorous crude extract after evaporation of the solvent. The main compounds 3,5-diisobutyl-l,2,4-trithiolane (7) and 4,7-diisobutyl-l,2,3,5,6-pentathiepane (18) as well as seven minor compounds were isolated after column chromatography on silica gel. The compounds 7 and 12 were additionally purified by gas chromatography. The yields of 7 and 18 in the strain Vc6bk reached nearly 1 mg/l. The remaining compounds were identified...