Probing the Stereospecificity and Chemospecificity of Polyketide Thioesterases

Abstract

Macrocyclization is a synthetically challenging step in the total synthesis of natural products. The success of chemical approaches such as the Corey-Nicolaou, Yamaguchi and Keck macrolactonization is heavily based on the confirmation and stereochemistry of the substrate. While there have been some advances in computational modeling, it has been difficult to predict whether the above-mentioned reactions will work. We have begun characterizing polyketide thioesterase catalytic activity and substrate tolerance to find more efficient and dependable routes towards macrolactonization and macrolactamization.