Biosynthesis of Cladospirone Bisepoxide, A Member of the Spirobisnaphthalene Family

Abstract

The biosynthesis of cladospirone bisepoxide (1) was investigated by feeding ¹³C-labeled acetate to growing cultures of the fungus Sphaeropsidales sp. (strain F-24'707). ¹³C NMR spectral analysis demonstrated the polyketide origin of both naphthalene units. The origin of two epoxide oxygens was confirmed as from air by cultivation of the strain in an ¹⁸O₂-enriched atmosphere. The [¹⁸O]incorporation pattern into palmarumycin C₁₂ (11), the putative precursor of 1 led to the hypothesis that the carbonyl oxygen of 1 is derived from water by exchange of an oxygen atom. Inhibition of the biosynthesis of 1 with tricyclazole, an inhibitor of the 1, 8-dihydroxynaphthalene (DHN) melanin biosynthesis, confirmed the connection of both biosynthetic pathways.