CHAPTER 15 – Avermectins

Publisher Summary This chapter provides an overview on the avermectins. Avermectins are potent antiparasitic compounds with a broad spectrum of activity against nematodes and arthropods. Although similar in structure to the antibacterial macrolides and antifungal macrocyclic polyenes, avermectins lack antibacterial and antifungal activity. They bind to a specific, high-affinity site present in nematodes but not in vertebrates. The biochemical and genetic studies help to establish that avermectin biosynthesis results from an interaction of the primary and secondary metabolic pathways of S. avermitilis. The acyl precursors are formed from primary pathways. The biosynthesis of dTDP-oleandrose and avermectin aglycones is mediated by avr-encoded enzymes. The biosynthesis of avermectin aglycone requires an elaborate PKS consisting of multiple, multifunctional polypeptides with at least 56 distinct domains. Although genetic studies have pinpointed most of the functions necessary for avermectin biosynthesis, neither the regulatory genes nor the multiple cyclase genes have been identified. Moreover, nearly all of the avermectin gene products are yet to be characterized biochemically.