Biocatalytic Approaches for the Synthesis of Bioactive Molecules

最近的研究表明，在人口老龄化和医疗保健成本不断增加的情况下，促进功能成分和营养保健品的发展有助于支持和改善整体公共卫生。考虑到功能性产品代表了一个新兴的细分市场，该领域的创新将有助于农业食品部门，这是加拿大第二大产业，在竞争日益激烈的市场中保持其地位。在此背景下，该研究计划的长期目标是开发创新的生物催化方法，以合成生物活性分子，并在食品工业和医疗保健领域具有潜在的应用。目前，该研究项目的方向是研究创新的酶糖基化方法的发展，并推进对糖基转移酶在高产量合成定制寡糖/多糖中的作用机制的理解，在短期内，特别关注新型ß-(2-6)-同源和异聚低聚糖（FOSs）和levans的合成。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正日益被认识到，对这些生物活性分子健康属性的理解取得了进展，因此需要高效的合成途径。左旋蔗糖酶（Levansucrase， LS）催化的转果糖化反应已经被我的团队和其他人证明是一个潜在的途径，可以得到各种homo/hetero FOSs和β-(2-6)-levans。然而，迄今为止，这条路线在工业层面甚至在准备规模上仍未得到开发。需要进一步的研究来克服这种方法的挑战和局限性。为了解决这一问题，拟议研究计划的短期目标包括以下几个方面：(1)通过探索细菌生物多样性发现具有更好催化性能的LSs并研究其特性；(2)开发创新方法，在分子水平上改善和调节LS特性，以更好地适应特定应用；(3)理解和利用LSs/其他生物催化剂之间的协同作用来开发多酶系统。从这个项目中产生的知识库将有助于碳水化合物合成领域的进步。特别是，对左旋蔗糖酶催化转果糖基化的复杂动力学的理解将为更好地应用这种糖基化策略提供基础。该研究项目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，许多高素质的人才将在这一新兴领域培养五年。

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 ß-(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 β-(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.