SBIR Phase II: Enzyme-based Magnetic Catalysts for Active Pharmaceutical Intermediates (APIs) Manufacturing

这个小企业创新研究第二阶段项目的更广泛的商业潜力是用于固定酶的新材料和工艺的商业开发。该项目的目标是将酶作为催化剂用于生产活性药物中间体（API）。使用酶生产药物具有降低成本、复杂性和提高生产这些产品的效率的潜力。这种绿色、经济高效且可规模化的氧化固定化酶将通过提高生产效率和经济性以及最小化对环境的不利影响而使制造商受益。该技术可以使良性氧化酶在商业上具有竞争力，取代昂贵的贵金属催化剂，有毒或其他用于API生产过程的危险化学品。这项技术的工业应用可能远远超出制药竞技场。该第二阶段研究项目的技术目标是（1）开发用于生产高价值商业活性药物成分（API）的氧化酶构建体和生物催化方案，（2）开发和生产磁性大孔支架，以及（3）改进商业反应器的操作，用于连续流生产或使用这些固定化酶的磁性催化剂改造现有生产工艺。该项目使固定化成为选择过程的一部分：通过三个层次的创新工程酶固定化，可以选择酶以其固定化形式的真正潜力：将商业上可获得的或第三方工程酶捕获到磁性纳米团簇中;产生稳定磁性纳米团簇组装体的高表面积支架，提供了磁性地保持纳米团簇组件悬浮的成本和工艺优点。 该项目的重点是一种来自氧化还原酶家族的高潜力、描述充分且可商购的酶，该酶将用于制药行业酶生产商和酶终端用户合成药物中间体。

The broader commercial potential of this Small Business Innovation Research Phase II project is the commercial development of novel materials and processes for the immobilization of enzymes. The project is targeting enzymes as catalysts to be used in the manufacturing of active pharmaceutical intermediates (API). The use of enzyme for the production of pharmaceuticals has the potential to reduce cost, complexity and improve efficiency in making these products. The green, cost-efficient and scalable oxidative immobilized enzymes will benefit manufacturers by improving their production efficiencies and economics as well as minimizing adverse environmental impact. The technology could make benign oxidative enzymes commercially competitive replacing expensive precious metal catalysts, toxic, or other hazardous chemicals used in the production processes for APIs. The industrial applications for this technology could be broad well beyond the pharmaceutical arena. The technical objectives of this Phase II research project are to (1) develop oxidative enzyme constructs and biocatalytic schemes for the production of high-value commercial active pharmaceutical ingredients (APIs), (2) develop and produce magnetic macroporous scaffolds, and (3) improve operation of commercial reactors for continuous flow manufacturing or retrofit existing production processes using these magnetic catalysts with immobilized enzymes. This project enables immobilization to become a part of the selection process: enzymes can be selected for their true potential in their immobilized form by engineering enzyme immobilization with three levels of innovation: entrap commercially-available or third-party engineered enzymes into magnetic nanoclusters; create high-surface area scaffolds that stabilize the magnetic nanocluster assemblies, providing cost and process advantages of maintaining the nanocluster assemblies in suspension magnetically. This project is focusing on a high-potential, well-described and commercially available enzyme from the oxidoreductase family that will be used the synthesis of drug intermediates by enzyme-producers and enzyme-end users in the pharmaceutical sector.