Fungal type I polyketide synthases

Fungi produce a wide variety of biologically active compounds, a large proportion of which are produced by the polyketide biosynthetic pathway. Fungal polyketides comprise a very large and structurally very diverse group, and many display important biological activities, including lovastatin, aflatoxins, and strobilurins. These are produced by very large multifunctional iterative enzymes, the iterative type I polyketide synthases (PKSs) whose closest structural and functional analogues are the mammalian fatty acid synthases. Although fungal polyketides were one of the first classes of secondary metabolites to be subject to extensive biosynthetic studies, they remain the least studied and understood at the enzyme level. This chapter presents an overview of methodologies that have been applied to in vivo and in vitro genetic and biochemical studies on the PKSs responsible for both aromatic and highly reduced polyketide metabolites, and which are providing an improved insight into how these highly complex enzymes function.