SBIR Phase I: Alcohol Resistant Enzymes through High-Throughput Combinatorial Protein-Polymer Conjugate Synthesis

SBIR 第一阶段：通过高通量组合蛋白质-聚合物缀合物合成抗酒精酶

• 批准号: 1746912
• 负责人: Antonina Simakova
• 金额: $ 22.5万
• 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: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1746912&HistoricalAwards=false
• 关键词: SBIR; Phase; Alcohol; Resistant; Enzymes

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 work with 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 synthetic 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 advanced nano-armored enzyme with improved properties such as solvent and temperature resistance, and modulated activity. Creating such novel stabilized enzymes will result in more efficient commercial utilization of enzymatic catalysis which requires less energy, utilizes less hazardous reagents, and generates less waste while generating valuable products such as chemicals, biofuels, and pharmaceuticals.This SBIR Phase I 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 one has to consider methods of scaling 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 gained properties. The initial target application of the proposed research is focused on the industrial 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 what kind of protein properties can be gained through polymer modification, thereby establishing this method for industrial applications.

该小企业创新研究 (SBIR) 项目的更广泛影响/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使用，并且通常需要更广泛的开发才能适应工业或制药制造。该 SBIR 项目将展示如何利用合成聚合物的稳定性来提高酶的性能。酶具有精确、独特的结构和功能，这对于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先进的纳米装甲酶，其具有改进的特性，例如耐溶剂性和耐温性以及可调节的活性。创造这种新型稳定酶将导致酶催化更有效的商业利用，需要更少的能源，使用更少的危险试剂，产生更少的废物，同时产生化学品、生物燃料和药品等有价值的产品。该 SBIR 第一阶段项目建议开发一种组合合成装置，可以对具有所需特性（例如温度、pH 或有机溶剂稳定性）的酶-聚合物缀合物进行高通量筛选。迄今为止，仅将低通量合成和表征方法应用于酶-聚合物缀合物的制备，这将开发限制为每种蛋白质仅进行几种类型的聚合物修饰，并且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用的各种聚合物，人们必须考虑扩大鉴定最佳性能酶-聚合物缀合物的方法。这将通过酶-聚合物缀合物的高通量合成和所得特性的高通量筛选相结合来实现。该研究的初步目标应用集中在工业生物催化。高通量方法的应用不仅会缩短研发周期，而且会加速我们对通过聚合物修饰可以获得什么样的蛋白质特性的基础知识的发展，从而建立该方法的工业应用。