The still largely unexplored structural and chemical diversity of natural products is unmatched by synthetic method and continues to be the most successful source for the discovery of novel scaffolds with important biological activities. We are exploiting and investigating the selectivity and specificity of the biosynthetic machineries that make these complex compounds to create ways of synthesizing diverse natural products or their core scaffolds for further synthetic modification. To do so, we are fitting microbial cells with new biosynthetic abilities using metabolic and genetic pathway engineering strategies together with evolutionary and rational protein engineering strategies to alter and study biosynthetic activities. The ability to rapidly assemble genetic components and synthesize DNA cheaply allows the redesign of biological systems for the execution of new functions. We introduce complex new metabolic abilities into microbial cells to generate designer bacteria with useful new properties