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

这个小型企业创新研究(SBIR)项目的更广泛的影响/商业潜力是建立一种广泛适用的突破性生物催化技术，以生产一类重要的化合物，称为手性环丙烷。环丙烷是用于合成药物、作物保护剂和高价值电子化学品的关键中间体。使用这种技术获得的产品每年的市场总额超过100亿美元。如果成功，正在开发的技术将创建更安全、更清洁、更可持续的重要化学产品路线，通过减少生产步骤、降低所需资本投资和显著减少浪费来降低成本。用更有效和更可持续的酶催化步骤取代现有的化学路线也将提高用于制造药物和作物保护化学品的许多先进医药中间体的纯度。STTRI期项目建议建立在第一阶段的结果基础上，在第一阶段中，使用一种新型的工程酶开发了一种高效的生物催化工艺来生产药物替卡格雷。我们将创建一套扩展的环丙烷化生物催化剂，能够作用于更广泛的起始材料，从而扩大这一新的酶反应的范围和用途。我们将完成替卡格雷关键中间体生产工艺的开发和商业化，并启动开发新型生物催化剂以生产抗病毒药物LE中间体的工作。我们还将开发一套酶并将其商业化，药物发现化学家可以使用这些酶来为下一代药物建立有效的路线。

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.