DISTRIBUTION OF ZARAGOZIC ACIDS (SQUALESTATINS) AMONG FILAMENTOUS ASCOMYCETES

The search for squalene synthase inhibitors of microbial origin has resulted in the discovery of a new class of fungal metabolites, the zaragozic acids (squalestatins). During our survey of representatives of most major groups of fungi and filamentous bacteria, the zaragozic acids were not found in prokaryotes, Zygomycotina, or Basidiomycotina. All the fungal producers encountered to date are Ascomycotina, their related anamorphic states or sterile organisms with ascomycete affinities. Members of at least 11 different taxa of fungi are capable of making zaragozic acids. Zaragozic acid A (squalestatin 1) appears to be the most prevalent among the different fungal taxa. In several cases we have observed production in multiple strains of the same species; for example, nearly all strains of Sporormiella intermedia, that we have examined, produce zaragozic acid B. The discovery of the zaragozic acids illustrates how knowledge of fungal biology and biochemistry can enhance the search for new chemical entities. Simultaneous screening of fungi from diverse phylogenetic and ecological origins was emphasized to discover new zaragozic acids rather than simply relying on organisms from a single kind of substratum from geographically disparate sources.