ABSTRACT
This chapter outlines the basic organizational logic underpinning several of the most important and best-understood biosynthetic processes responsible for bioactive natural products. It considers how an understanding of the biochemistry and genetics involved in these processes has led to initial success and also revealed future possibilities in combinatorial biosynthesis. The chapter discusses the engineering of the biosynthetic machinery that produces polyketides (PK) and the nonribosomal peptides. It focuses on opportunities for creating PK structural diversity through biosynthesis and chemobiosynthesis. All PKs are united by a basic structural pattern originating from two-carbon units containing alternating oxygenated and unoxygenated carbons. Researchers have begun to take advantage of the emerging understanding of how the polyketide synthases (PKS) are organized and operate in order to engineer increased chemical diversity into PK structures. The logic and hierarchy of nonribosomal peptide biosynthesis is highly complementary to that of the PKS system.
