Biocatalysis

This chapter presents a brief summary of the state of the art of enzyme engineering. It then highlights several processes in which a biocatalytic process has been reported to have displaced a traditional chemical manufacturing route based on improved sustainability and economic metrics. The demonstrations of the creation of novel biocatalysts combined with state of the art enzyme engineering technology will lead to a broadening of the scope of biocatalysis and its application to the efficient synthesis of pharmaceuticals. There is a tremendous body of literature on the synthesis of pharmaceutical small-molecule active pharmaceutical ingredients (APIs) using biocatalysis, but only a very small fraction of these have been practiced at large scale. In an initial directed evolution program, variants were created by saturation mutagenesis of the active site region and by error-prone Planning and Community Right (PCR) using a zone clearing plate assay in which the product simvastatin inhibited the growth of Neurospora crassa.