Browsing by Author "Walker, M."

The 14-membered macrolide, mutolide (1), was discovered by chemical screening of the culture broth of the fungus F-24'707y, obtained after UV mutagenesis of the wild type strain, which normally produces the spirobisnaphthalene cladospirone bisepoxide (2). The structure of 1 was established by detailed spectroscopic analysis, X-ray analysis and derivatisation. The biogenetic origin of the carbon skeleton and the hydroxy groups was verified by feeding sodium [1-C-13]acetate and O-18(2) to growing cultures of the fungus. Macrolide 1 is generated from acetate/malonate only. The unexpected change of the normal metabolite pattern of this strain is discussed, and proves the value of the OSMAC method.

Variation of the culture conditions - static surface cultures in particular - of the fungus Sphaeropsidales sp. (strain F-24'707), which produces cladospirone bisepoxide (1), led to the isolation of eight new spirobisnaphthalenes - the cladospirones B to I (8-15) -together with seven known representatives of this class of secondary metabolites. Cladospirones C (9) and D (11) show antibiotic activity against bacteria and algae. The structures of cladospirone B (8) and E (12) were confirmed by X-ray structure analysis. Cladospirones C (9) and G to I (10, 14-15) represent new members of the spirobis-naphthalene family, thanks to their hydroxylation patterns. Moreover, they underline the extraordinary status of this interesting class of compounds as the most diverse secondary metabolites, allowing for their small number of carbon atoms, described to date. Almost all possible permutations of stereochemistry and oxygen substitution pattern on the C-10 skeleton are produced by different fungi.

The simocyclinones D4 (1) and D8 (2), members of a novel class of antibiotics, were isolated from the mycelial extract of Streptomyces antibioticus Tu 6040 and consist of angucyclinone, deoxysugar, octatetraene dicarboxylate and aminocoumarin structural elements. The structure elucidation was done by one and two dimensional NMR experiments, and other spectroscopic methods in combination with incorporation experiments using C-13 labelled precursors.

Two novel angucyclinone-type antibiotics, simocyclinones D4 and D8, were detected in the mycelium extract of Streptomyces antibioticus Tu 6040 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening. The compounds show antibiotic activities against Gram-positive bacteria and cytostatic effects on various tumor cell lines.

Simocyclinones, a novel group of angucyclinone antibiotics, are produced by Streptomyces antibioticus Tu 6040. The compounds show antibacterial and antitumor properties. In submerged cultivation, the production of simocyclinones is strongly dependent on the carbon and nitrogen sources used in a chemically defined medium. Productivity of distinct components and diversity of simocyclinone compounds are influenced by the medium composition. Four series of simocyclinone compounds were detected by high-performance liquid chromatography (HPLC) diode array detector (DAD) and HPLC electrospray ionization (ESI) mass spectrometry (MS) analysis, isolated and the structures determined by nuclear magnetic resonance (NMR) techniques. Under optimized conditions, simocyclinone D8 was produced in an amount of 300 mg l(-1) and simocyclinone C4 in a concentration up to 50 mg l(-1).