Structure, function, and engineering of plant polyketide synthases

Type III polyketide synthases (PKSs) catalyze sequential condensations of acyl-CoA thioesters to generate a variety of polyketide scaffolds with remarkable structural diversity and significant biological activities. These enzymes share a similar thiolase fold and use a common catalytic triad for the polyketide chain elongation and cyclization reactions. Structural and biochemical analyses of type III PKSs revealed that the functional diversity of these highly homologous enzymes is attributable to subtle changes in their active site volumes and architectures. The accumulated knowledge of their detailed catalytic versatility and mechanisms provides a platform for enzyme engineering via structure-guided approaches for the generation of unnatural novel polyketides. In this chapter, the methods for identification, biochemical characterization, and structure-guided engineering of polyketide synthases will be described in detail, along with brief overviews of the structures and functions of these enzymes.