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.

这项小型企业创新研究（SBIR）项目的更广泛的影响/商业潜力包括促进白人生物技术领域的发展，该领域利用酶来创造有价值的工业产品。作为生物分子，酶比常规化学物质更难操纵，并且通常需要更广泛的开发，然后才能适应工业或药物制造。该SBIR项目将证明如何使用特殊的合成材料（称为聚合物）的稳定化可以改善酶的性能。酶的特征是精确，独特的结构和功能，这反过来又对它们在复杂化学反应的催化中的作用至关重要。另一方面，合成聚合物尽管结构较少，但可以理性地设计以承受或响应化学，热或生物学条件。酶和合成聚合物的协同融合会导致高级酶具有改进的化学性质，从而为诸如化学品，生物燃料和药品等有价值产品的新制造工艺提供了新的制造过程。这些过程应需要更少的能量，利用更少的危险试剂，并减少浪费。该SBIR II期项目提议开发一种组合合成装置，该设备可以用所需的特性（例如，温度，pH-或有机溶剂稳定性）对酶 - 聚合物结合物进行高通量筛选。迄今为止，仅将低通量的合成和表征方法应用于酶聚合物偶联物的制备，将开发限制为每种蛋白质的多种多样的聚合物修饰，并取决于随机猜测，以选择测试的变体。因此，为了完全受益于目前在市场上可用的各种聚合物集中，重要的是开发方法以扩展最佳执行酶 - 聚合物偶联物的识别。这将通过将酶 - 聚合物共轭物的高通量合成和所达到特性的高通量筛选结合在一起来实现。拟议研究的目标应用集中在药物生物催化上。高通量方法的应用不仅会导致更快的研发周期，而且还将加速我们对识别蛋白质特性的基本知识的发展，从而通过聚合物修改来实现，从而为工业应用建立了这种方法，从而为NSF的法定任务提供了反映的法定任务，并通过评估了基金会的范围，并通过评估了基金会的范围。