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: 371898-2010
• 负责人: Karboune, Salwa
• 金额: $ 2.33万
• 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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=550131
• 关键词: Biocatalytic; approaches; synthesis; bioactive; molecules

The proposed research program investigates innovative biocatalytic approaches toward the development of functional ingredients and nutraceuticals. In the short term, the primary focus of this program is on the development of novel enzymatic glycosylation strategies for efficient synthesis of non-digestible oligosaccharides whose benefits, in supporting intestinal health and reducing the risk of cancers, are being increasingly recognized. Novel fructooligosaccharides (FOSs), headed with different pentoses or polyols instead of a glucosyl moiety, have been identified as potential candidates. These new FOSs may conceivably possess new immunomodulatory capacity and antiadhesive activity against pathogens that are not present in the current FOS generation. Although levansucrases (LSs) are being increasingly recognized for their potential to catalyze the synthesis of novel FOSs, their availability and their operational stability are still limited. Initial efforts have been focused on the induction and the recovery of novel LSs from thermophilic microbial sources. To provide a rational basis for a better modulation of the actions of LSs, an important part of the proposed research will focus on the investigation of the mechanism by which these enzymes function. The driving forces that control the thermodynamic equilibrium of LS-catalyzed transfructosylation will also be studied for a greater-yield synthesis of well-defined FOSs. With the aim of enabling easy modulation of the transfructosylation processes, the immobilization of LSs on nanomaterial supports will be studied, emphasizing the relationships between the features of nanomaterials and the efficiency of LSs. The rational combination of immobilization and molecular imprinting will be further explored to improve the LS selectivity. The produced FOSs will be characterized in terms of their structures and their biological activities. This challenging research program is of scientific importance as it will advance the knowledge in the emerging field of enzymatic glycosylation and provide a scientific-based ground for the development of biocatalytic processes at the industrial level for the synthesis of novel FOSs of a potential use as functional ingredients.

拟议的研究计划调查创新的生物催化方法对功能成分和营养保健品的发展。在短期内，该计划的主要重点是开发新的酶促糖基化策略，以有效合成不易消化的寡糖，其在支持肠道健康和降低癌症风险方面的益处正日益得到认可。以不同的戊糖或多元醇代替葡萄糖基部分的新型低聚果糖（FOS）已被确定为潜在的候选物。这些新的FOS可能具有新的免疫调节能力和抗粘附活性，对病原体不存在于目前的FOS一代。尽管果聚糖蔗糖酶（LS）因其催化合成新型FOS的潜力而日益被认可，但其可用性和操作稳定性仍然有限。最初的努力集中在从嗜热微生物来源诱导和回收新型LS上。为了更好地调节LS的作用提供合理的基础，拟议研究的一个重要部分将集中在研究这些酶发挥作用的机制上。控制LS催化转果糖基化的热力学平衡的驱动力也将被研究，以更高的收率合成定义明确的FOSs。为了使转果糖基化过程易于调节，将研究LS在纳米材料载体上的固定化，强调纳米材料的特征与LS的效率之间的关系。将固定化技术与分子印迹技术合理结合，以提高LS的选择性。所产生的FOS将根据其结构和生物活性进行表征。这项具有挑战性的研究计划具有科学意义，因为它将推进酶促糖基化新兴领域的知识，并为工业水平的生物催化工艺的发展提供科学基础，以合成具有潜在功能性成分的新型FOS。