Natural Products in Chemical Biology

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POLYKETIDES IN FUNGI

THOMAS J. SIMPSON AND RUSSELL J. COX

School of Chemistry, University of Bristol, Bristol, United Kingdom

Fungi produce a wide variety of biologically active compounds. Among these compounds, the polyketides form a large and structurally diverse group. These compounds are synthesized by highly programmed, large iterative multifunctional proteins, which are called the polyketide synthases. This review describes the structure and biosynthesis of polyketide fungal metabolites and highlights recent work on the links between gene sequence, protein architecture, and biosynthetic programming for fungal polyketide synthases.

Polyketides have long been recognized as one of the most important classes of secondary metabolites (1). They occur in plants, bacteria, and marine organisms as well as in fungi. Fungal polyketides vary from the simplest monocyclic aromatic compounds, for example, orsellinic (1) and 6-methylsalicylic (6-MSA) (2) acids to polycyclic aromatics such as citrinin (3), alternariol (4), islandicin (5), deoxyherqueinone (6), and norsolorinic acid (7). Although initially associated with the formation of aromatic compounds, many polyketides are nonaromatic (e.g., the macrolide decarestrictine D (8), long-chain polyfunctional molecules exemplified by T-toxin (9) and the decalins, lovastatin (10), and compactin (11)). Many other metabolites consist of an aromatic ring attached to a more highly reduced moiety (e.g., zeralanenone (12), dehydrocurvularin ( ...