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 spectroscopic methods and CD measurements. The biosynthetic pathway to hypomycetin has been unveiled by feeding experiments with C-13-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.