A biosynthetic classification of fungal and streptomycete fused-ring aromatic polyketides

Polyketides are one of the largest and most structurally diverse classes of naturally occurring compounds, ranging from simple aromatic metabolites to complex macrocyclic lactones. Fungi and filamentous bacteria, particularly the actinomycetes, are major sources of polycyclic aromatic structures, wh ich include many clinically important antibiotics and other useful metaboli tes. These fused-ring polyketides are formed by the action of polyketide sy nthases (PKSs), which catalyse the assembly, folding and cross-linking of p oly-beta -ketoacyl intermediates. In view of the taxonomic gulf between the eukaryotic fungi and prokaryotic bacteria, it is not surprising that they are rarely found to produce structurally identical fused-ring metabolites. A review of [C-13(2)]acetate incorporation data has revealed consistent dif ferences in the reported cyclisation patterns, which require regiospecifica lly distinct cross-linking of otherwise identical linear polyketide precurs ors. This observation provides the basis for a structural and biosynthetic classification of microbial fused-ring polyketides, which has a number of u seful ramifications.