STTR Phase II: Enzymatic Synthesis of Chiral Cyclopropanes for Pharmaceutical Drug Synthesis and Agricultural Crop Protection Applications

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to establish a broadly applicable, breakthrough biocatalytic technology to produce an important class of compounds called chiral cyclopropanes. Cyclopropanes are key intermediates that are used in the synthesis of drugs, crop protection agents, and high-value electronic chemicals. Products accessible using this technology have markets totaling more than $10 billion annually. If successful, the technology under development will create safer, cleaner, more sustainable routes to important chemical products that will lower cost by reducing the number of production steps, lowering the required capital investment, significantly decreasing waste. Replacing existing chemical routes with the more efficient and sustainable enzyme-catalyzed steps will also improve the purity of many advanced pharmaceutical intermediates used in the manufacture of drugs and crop protection chemicals. This STTR Phase I project proposes to build on the results from Phase 1 in which a highly efficient biocatalytic process for the manufacture of the drug ticagrelor was developed using a novel, engineered enzyme. We will create an expanded set of cyclopropanation biocatalysts with the capability to act on a wider range of starting materials, thereby broadening the scope and utility of this new enzymatic reaction. We will complete the development and commercialization of the process for production of the key intermediate for ticagrelor and initiate work to develop novel biocatalysts to produce ley intermediates for anti-viral drugs. We will also develop and commercialize a set of enzymes that can be used by drug discovery chemists to establish efficient routes for next-generation drugs.