SBIR Phase II: High-Throughput Combinatorial Polymer Bioconjugates Synthesis and Application in Biocatalysis

SBIR第二期：高通量组合聚合物生物共轭物的合成及其在生物催化中的应用

• 批准号: 1927021
• 负责人: Antonina Simakova
• 金额: $ 74.28万
• 依托单位: BioHybrid Solutions LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1927021&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Throughput; Combinatorial

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project includes advancement of the field of white biotechnology, which utilizes enzymes to create valuable industrial products. As biological molecules, enzymes are more difficult to manipulate than conventional chemicals and often need more extensive development before they can be adapted to industrial or pharmaceutical manufacturing. This SBIR project will demonstrate how enzymes' performance can be improved using stabilization with special synthetic materials known as polymers. Enzymes are characterized by precise, unique structure and function, which is in turn essential for their role in catalysis of complex chemical reactions. Synthetic polymers, on the other hand, despite being less precisely structured, can be rationally designed to withstand or respond to chemical, thermal or biological conditions. The synergistic fusion of enzymes and synthetic polymers results in an advanced enzyme with improved chemical properties, leading to new manufacturing processes for valuable products such as chemicals, biofuels, and pharmaceuticals; these processes should require less energy, utilize fewer hazardous reagents, and generate less waste. This SBIR Phase II project proposes to develop a combinatorial synthesis device that can feed high-throughput screening of enzyme-polymer conjugates with desired properties (for instance, temperature, pH- or organic solvent stability). To date, only low-throughput synthesis and characterization methods have been applied to the preparation of enzyme-polymer conjugates, limiting development to only few types of polymer modification per protein and depending on stochastic guesswork to select the variants tested. Thus, in order to fully benefit from the diverse set of polymers currently available on the market, it is important to develop methods to scale the identification of optimally performing enzyme-polymer conjugates. This will be achieved through combination of high-throughput synthesis of enzyme-polymer conjugates and high-throughput screening of attained properties. The target application of the proposed research is focused on pharmaceutical biocatalysis. Application of a high-throughput method will not only result in faster research and development cycles, but also will accelerate our development of fundamental knowledge of identifying protein properties that can be achieved through polymer modification, thereby establishing this method for industrial applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力包括白色生物技术领域的进步，该领域利用酶来创造有价值的工业产品。作为生物分子，酶比传统化学品更难操作，在适用于工业或制药生产之前，通常需要更广泛的开发。这个SBIR项目将展示如何使用被称为聚合物的特殊合成材料来提高酶的性能。酶的特点是精确的，独特的结构和功能，这反过来又是必不可少的，它们在催化复杂的化学反应的作用。另一方面，合成聚合物尽管结构不太精确，但可以合理设计以承受或响应化学，热或生物条件。酶和合成聚合物的协同融合产生了具有改进的化学性质的先进酶，从而产生了化学品，生物燃料和药物等有价值产品的新制造工艺;这些工艺需要更少的能源，使用更少的危险试剂，并产生更少的废物。该SBIR第二阶段项目提出开发一种组合合成装置，该装置可以高通量筛选具有所需特性（例如，温度，pH或有机溶剂稳定性）的酶-聚合物缀合物。到目前为止，只有低通量的合成和表征方法已被应用到酶-聚合物缀合物的制备，限制了发展，只有少数类型的聚合物修饰每个蛋白质和依赖于随机猜测来选择测试的变体。因此，为了充分受益于目前市场上可获得的各种聚合物，重要的是开发方法来扩大最佳性能的酶-聚合物缀合物的鉴定。这将通过酶-聚合物缀合物的高通量合成和所获得的性质的高通量筛选的组合来实现。该研究的目标应用集中在药物生物催化。高通量方法的应用不仅会导致更快的研究和开发周期，而且还将加速我们对鉴定蛋白质性质的基础知识的发展，这些蛋白质性质可以通过聚合物修饰来实现，该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的评估，被认为值得支持。影响审查标准。