ABSTRACT

A scaffold is the basic structural element used as the starting point for the generation of chemical libraries. The biosynthetic origin and many functions of natural products require interactions with proteins. Natural products have evolved with a functional filter, which makes them ideal candidates for interactions with target proteins in drug discovery. Screening of proprietary libraries provides a unique opportunity for the identification of novel scaffolds. Such libraries contain either isolated natural products or complex samples based on fermentation broths. The chapter focuses on the production of natural product scaffolds by fermentation of microorganisms. The production of secondary metabolites by microorganisms is strongly influenced by growth conditions and nutritional factors such as carbon source, nitrogen source, minerals, trace elements, and vitamins. By genetic engineering, microorganisms can be optimized for the production of one single compound, and this can result in an increased product titer and a facilitated isolation procedure.