Biocatalytic Approaches for the Synthesis of Bioactive Molecules

合成生物活性分子的生物催化方法

• 批准号: RGPIN-2016-05042
• 负责人: Karboune, Salwa
• 金额: $ 2.99万
• 依托单位: McGill University
• 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=708609
• 关键词: Biocatalytic; Approaches; Synthesis; Bioactive; Molecules

Recent studies indicate that contributions to the development of functional ingredients and nutraceuticals can help support and improve the overall public health, which is timely given the aging of the population and the increasing cost of health care. Considering that the functional products represent an emerging market segment, innovations in this field will assist the agri-food sector, which is the second largest industry in Canada, in maintaining its position in an increasingly competitive marketplace. In this context, the long-term objective of the proposed research program focuses on developing innovative biocatalytic approaches toward the synthesis of bioactive molecules with potential applications in the food industry and for healthcare. Currently, this research program is directed toward investigating the development of innovative enzymatic glycosylation approaches and advancing the understanding of the mechanisms by which the glycosyl-transferases function for the high-yield synthesis of tailor made oligo/polysaccharides, with a particular focus, in the short term, on the synthesis of novel -(2-6)-homo and heterofructooligosaccharides (FOSs) and levans. Progress in the understanding of the health attributes of these bioactive molecules, whose potential benefits in terms of supporting intestinal health and reducing the risk of cancers are increasingly being recognized, has given rise to a need for efficient synthetic routes. Levansucrase (LS)-catalyzed transfructoslyation reaction has been proven by my group and others to be a potential route to a variety of homo/hetero FOSs and -(2-6)-levans. To date, however, this route has remained untapped at the industrial level and even on the preparative scale. Further research is needed to overcome the challenges and the limitations of this approach. To address this, the short-term objectives of the proposed research program consist of a linked approach to: (1) discover LSs with better catalytic properties through the exploration of bacterial biodiversity and study their properties; (2) develop innovative approaches to improve and modulate LS properties at the molecular level that can better suit specific applications; (3) understand and exploit synergism between LSs/other biocatalysts to develop multi-enzymatic systems. The knowledge base emerging from this program will contribute to the advancement of the field of carbohydrate synthesis. In particular, the understanding of the complex kinetics involved in the levansucrase-catalyzed transfructosylation will provide the basis for a better application of this glycosylation strategy. This research program will also contribute to the development of productive multi-enzymatic systems of great potential for industrial applications. As a research training program, many highly qualified personnel will be trained over the five years in this emerging field.

最近的研究表明，对功能性成分和营养保健品的开发做出贡献可以帮助支持和改善整体公共卫生，这是人口老龄化和医疗保健成本增加的及时因素。考虑到功能性产品代表了一个新兴的细分市场，这一领域的创新将有助于农业食品部门，这是加拿大的第二大产业，在竞争日益激烈的市场中保持其地位。在这种情况下，拟议的研究计划的长期目标侧重于开发创新的生物催化方法，以合成在食品工业和医疗保健中具有潜在应用的生物活性分子。目前，该研究计划旨在研究创新的酶促糖基化方法的发展，并促进对糖基转移酶用于高产量合成定制寡糖/多糖的机制的理解，特别关注在短期内合成新型-（2-6）-均和杂果寡糖（FOS）和果聚糖。这些生物活性分子在支持肠道健康和降低癌症风险方面的潜在益处越来越多地被认识到，在理解这些生物活性分子的健康属性方面的进展已经引起了对有效合成途径的需求。果聚糖蔗糖酶（Levansucrase，LS）催化的转果糖基化反应已被本课题组和其他研究人员证明是一条潜在的合成各种同/杂FOS和-（2-6）-果聚糖的途径。然而，迄今为止，这条路线在工业水平上甚至在制备规模上仍然没有开发。需要进一步研究，以克服这种方法的挑战和局限性。为了解决这个问题，拟议的研究计划的短期目标包括一个相关的方法：（1）通过探索细菌生物多样性发现具有更好催化性能的LS，并研究它们的性能;（2）开发创新方法，以改善和调节LS在分子水平上的性能，使其更适合特定的应用;（3）了解并利用LS/其他生物催化剂之间的协同作用来开发多酶系统。从这个程序中出现的知识基础将有助于碳水化合物合成领域的进步。特别是，复杂的动力学参与果聚糖蔗糖酶催化转果糖基的理解将提供一个更好地应用这种糖基化策略的基础。该研究计划还将有助于开发具有巨大工业应用潜力的生产性多酶系统。作为一项研究培训计划，将在五年内培训这一新兴领域的许多高素质人员。