Structure and Biosynthesis of Mutolide, a Novel Macrolide from a UV Mutant of the Fungus F-24′707

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 [1-13C]acetate and 18O2 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.