Biocatalytic Activation of Macromolecular Building Blocks

大分子构件的生物催化活化

• 批准号: RGPIN-2017-06789
• 负责人: Master, Emma
• 金额: $ 2.4万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=712456
• 关键词: Biocatalytic; Activation; Macromolecular; Building; Blocks

Greater use of all bioresource fractions will be critical to an invigorated forest sector that plays a central role in Canada's growing bioeconomy and national commitments to reduced carbon emissions. Moreover, seizing this opportunity will realize Canada's potential to supply global bioproduct markets while capitalizing on its historical investment in infrastructure and know-how in bioresource use and management. In addition to innovative use of renewable biomass feedstocks, bio-economies are exemplified by increased application of sustainable, biologically catalyzed processes. Indeed, the importance of microbial enzymes to expanding the range of products that can be made from plant-derived biomass is well recognized. However, biotechnologies to date largely focus on the deconstruction of the bioresource for microbial fermentation or chemical conversion to commodity fuels and chemicals. While products derived from primary sugars and monolignols will be necessary for capturing the full potential of renewable plant biomass, these products relinquish the inherent functional attributes to the starting biomass resource. The potential of biocatalysts to upgrade (rather than degrade) biopolymer chemistries presents an alternative to the practice of “deconstruct to reconstruct” which dominates current biorefinery concepts. Accordingly, rather than target enzymes for lignocellulose deconstruction, the proposed program will focus on the discovery and application of enzyme systems that activate underused hemicellulose fragments, permitting their reassembly into biopolymer structures that capture the innate function of this major biomass fraction, leading to bio-based crosslinkers, surface coatings, and rheology modifiers. The emphasis on biocatalytic routes to activated building blocks will help ensure that both end-products and synthesis pathways are sustainable, while also harnessing the catalytic precision offered by a biocatalytic approach. The following four integrated steps will be followed to achieve the program goals: 1) bioinformatics analyses to prioritize carbohydrate oxidase and transaminase selections and inform protein engineering strategies; 2) production of protein targets using high-throughput and recombinant approaches; 3) biochemical characterization of isolated enzymes and reaction products to identify complementary and compatible enzyme systems, and 4) application of established coupling pathways to demonstrate the potential to re-assemble the enzymatically activated oligomers. In addition to accelerating the application of genomics research in the bioproducts sector, the proposed research will advance emerging trends in cell-free biocatalytic cascades, and create new tools to facilitate the design and development of novel bio-based materials from underused biomass fractions.

更多地利用所有生物资源部分将对充满活力的森林部门至关重要，因为森林部门在加拿大日益增长的生物经济和国家减少碳排放的承诺中发挥着核心作用。此外，抓住这一机会将实现加拿大向全球生物产品市场供应的潜力，同时利用其在生物资源使用和管理方面对基础设施和技术的历史投资。 除了可再生生物质原料的创新使用外，生物经济的例子是更多地应用可持续的生物催化过程。事实上，微生物酶对于扩大从植物来源的生物质制成的产品范围的重要性得到了很好的认识。然而，到目前为止，生物技术主要侧重于解构用于微生物发酵或将化学转化为商品燃料和化学品的生物资源。虽然从初级糖和单醇衍生的产品对于充分挖掘可再生植物生物质的潜力是必要的，但这些产品放弃了原始生物质资源的固有功能属性。 生物催化剂升级(而不是降低)生物聚合物化学的潜力为主导当前生物精炼概念的“解构重建”实践提供了另一种选择。因此，拟议的计划将专注于激活未被充分利用的半纤维素片段的酶系统的发现和应用，而不是针对木质纤维素解构的酶系统，允许它们重新组装成生物聚合物结构，从而捕获这一主要生物质组分的固有功能，从而产生生物交联剂、表面涂层和流变学改进剂。对生物催化途径的重视将有助于确保最终产品和合成途径都是可持续的，同时也利用生物催化方法提供的催化精确度。为了实现计划目标，将遵循以下四个综合步骤：1)生物信息学分析，以确定碳水化合物氧化酶和转氨酶选择的优先顺序，并为蛋白质工程策略提供信息；2)使用高通量和重组方法生产蛋白质靶标；3)分离酶和反应产物的生化特性，以确定互补和相容的酶系统；以及4)应用已建立的偶联途径，展示重新组装酶激活的寡聚体的潜力。除了加速基因组学研究在生物制品领域的应用外，拟议的研究还将推动无细胞生物催化级联的新趋势，并创造新的工具，促进利用未充分利用的生物质馏分设计和开发新型生物基材料。