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: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630604
• 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 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.

最近的研究表明，对功能成分和营养食品的开发做出贡献可以帮助支持和改善整体公共健康，这在人口老龄化和医疗保健成本不断上升的情况下是及时的。鉴于功能性产品属于新兴市场，这一领域的创新将有助于作为加拿大第二大产业的农业食品部门在竞争日益激烈的市场中保持其地位。在此背景下，拟议研究计划的长期目标集中在开发创新的生物催化方法，以合成具有潜在应用于食品工业和医疗保健的生物活性分子。目前，这项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在定制寡糖/多糖的高产合成中作用的机制的理解，特别是在短期内，特别关注新的？(2-6)-高聚果糖和杂果寡糖(FOSS)和Levans的合成。在了解这些生物活性分子的健康属性方面取得的进展，其在支持肠道健康和降低癌症风险方面的潜在好处越来越被认识到，这引发了对有效合成路线的需求。左旋蔗糖酶(LS)催化的跨果糖裂解反应已经被我的团队和其他人证明是一条合成各种同/异FOSS和β-(2-6)-Levans的潜在途径。然而，到目前为止，这条路线在工业层面，甚至在准备规模上仍未被开发。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一种相互关联的方法，以：(1)通过探索细菌生物多样性发现具有更好催化性能的LS并研究其性质；(2)开发在分子水平上改进和调节LS性质的创新方法，以更好地适应特定应用；(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，了解左旋蔗糖酶催化的果糖转移反应的复杂动力学将为更好地应用这一糖基化策略提供基础。这项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，许多高素质的人才将在这一新兴领域的五年内得到培训。