Polyketides, combinatorial biosynthetic addition

Tlie development of combinatorial biosynthetic shategies, in which components of different polyketide patliways aie combined to generate new polyketides, has attracted interest as a new dmg discovery tool. Extension of previous approaches focused on combinations of different polyketide synthase components to inclusion of patliways that generate different polyketide staiter units provides an additional element of shiictural diversity. 

In this chapter, we will introduce an exciting class of natural product biosynthetic enzymes, the modular synthases, as well as their associated enzyme partners. We will discuss the use of metabolic engineering as a tool for small-molecule discovery and development, both through directed fermentation and combinatorial biosynthesis. In addition, we will review six classes of partner enzymes involved in the modification of polyketide (PK) and nonribosomal peptide (NRP) natural products. We believe that these enzymatic transformations hold great opportunities for synthetic chemists and will serve as the foundation for a new trend in both discovery and process chemistry. 

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