Structure guided approaches toward exploiting and manipulating nonribosomal peptide and polyketide biosynthetic pathways

Nonribosomal peptide and polyketide natural products are structurally diverse small molecules synthesized on complex enzyme assemblies. The ability to rationally engineer secondary metabolic pathways is a promising approach to novel therapeutics. Atomic resolution structures of biosynthetic enzymes provide information on active site architecture and macromolecular assembly that can aid in the engineering of new compounds. This review surveys recent applications toward biosynthetic engineering of natural products guided by structural biology.

► Using structure to guide natural product bioengineering is an emerging strategy. ► Recent reports related nonribsomal peptide and polyketide pathways are reviewed. ► Studies have provided significant approaches to generating novel small molecules.