Hydrolases are valuable industrial biocatalysts used to prepare optically pure compounds. Despite advantages, these enzymes are restricted to a maximum single pass product yield of 50% with racemic substrates. Substrate specific racemases offer the potential to achieve 100% yield without recycling if used in situ with hydrolases in dynamic kinetic resolutions. However, few examples of industrially appropriate racemases have been described. Ingenza proposes to use in vivo selections to isolate and develop novel racemases and establish dynamic kinetic resolution as a more general method for synthetic process chemistry. The initial focus will be the isolation of N-acylamino acid racemases for use with L- or D-aminoacylases to prepare unnatural amino acids and amines. Such compounds are requisites as synthons for antiviral and antineoplastic drugs. New pharmaceuticals from anticipated advances in proteomics will likely increase demand for this technology. Ingenza proposes to develop a toolbox of racemases and an efficient, scaleable technologyfor use in organic synthetic reactions. Phase I will show feasibility of the selective approach in isolating novel racemases. In Phase II we will optimize enzyme properties and application as applied biocatalysts. In Phase III, we will commercialize the technology for use by synthetic organic chemists and pharmaceutical manufacturers.
Thesaurus Terms: aminohydrolase, chemical synthesis, enzyme activity, enzyme substrate complex, isomerase, stereoisomer, technology /technique development aminoacid, directed evolution, genetic library, phosphopyruvate hydratase Escherichia coli, mutant
