Hypomycetin - an antifungal, tetracyclic metabolite from Hypomyces aurantius: Production, structure and biosynthesis

As part of a screening programme a new antifungal substance, hypomycetin, has been isolated from the mycophilic fungus Hypomyces aurantius. Its tetracyclic structure, including the absolute configuration, has been established by spectro-scopic methods and CD measurements. The biosynthetic pathway to hypomycetin has been unveiled by feeding experiments with ¹³C-labelled precursors, followed by extensive NMR analyses. The extent of its relationship to viridicatumtoxin, a known, structurally similar fungal metabolite, and to the tetracyclic Streptomyces antibiotics, such as tetracycline and various congeners, is discussed in terms of biosynthetic origins. A polyketide folding mode, different from that involved in the biosynthesis of the tetracyclines, has been documented as the starting point on the path to hypomycetin.