Synthetic and mechanistic studies on fungal metabolic pathways: A guide to fungicide design

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Abstract
The polyketide biosynthetic pathway is responsible for the formation in microorganisms and plants of a vast array of diverse structures, many of which display important biological activity. A brief overview of the pathway, with emphasis on present problems and future developments, is presented and the impact of genetics on chemical and biochemical studies of polyketide biosynthesis is highlighted.Biosynthetic and mechanistic studies on three pathways are described, to illustrate how these studies may provide an insight into the mode of action of particular compounds, or how particular pathways may be inhibited. LL‐D253α is an antibiotic chromanone produced by a number of Phoma species. Stable isotope labelling studies have indicated the involvement of cyclopropylcyclohexadienyl intermediates in the formation of the hydroxyethyl side chain indicating a possible mode of action. Similar studies of monocerin indicate the involvement of quinone methide intermediates. A synthesis of monocerin, modelled on the biosynthetic pathway, is described. Scytalone and vermelone are intermediates on the pathway to melanin in certain pathogenic fungi, e.g. Pyricularia oryzae. Progress with biosynthetic studies on this pathway is described.