Genetic and Biosynthetic Studies of the Fungal Prenylated Xanthone Shamixanthone and Related Metabolites in Aspergillus spp. Revisited

Biosynthetic genes for the prenylated xanthone shamixanthone have been identified in the Aspergillus nidulans genome; based on assignment of putative functions from sequence analyses and selected gene deletions, a pathway was proposed leading from the anthraquinone emodin via the benzophenone carboxylic acid monodictyphenone and the xanthone emericellin to shamixanthone. Several aspects of this proposed pathway are inconsistent with previously identified biosynthetic intermediates: the anthraquinone chrysophanol and the benzophenone aldehyde derivatives arugosins F and A/B, isotopic labelling studies and chemical precedents. A new pathway is presented that provides a full rationale for the results of the gene deletion studies and reconciles them with previous biosynthetic results, and is in accord with established chemical and biosynthetic mechanisms. The importance of interpreting genetic information in terms of established biosynthetic events is discussed.