The chemical biology of modular biosynthetic enzymes

Abstract

Fatty acid synthase (FAS), polyketide synthase (PKS), and nonribosomal peptide synthetase (NRPS) modular biosynthetic enzymes are responsible for the production of a multitude of structurally diverse and biologically important small molecule natural products. Traditional biochemical and genetic studies of these enzymes have contributed substantially to the understanding of their underlying biosynthetic mechanisms. More recently these investigations have been aided by the skillful application of a combination of chemical and biological techniques to aid in overcoming the unique challenges associated with the enzymology of these large multifunctional enzymes. This critical review provides a historical context and details studies (through July 2008) which aim to identify and characterize these enzymes using synthetically and/or chemoenzymatically generated small molecule probes (233 references).