Enzymatic Synthesis of Sugar-Derived Biosurfactants Using Multifunctional Ionic Liquids

使用多功能离子液体酶法合成糖衍生生物表面活性剂

• 批准号: 10291051
• 负责人: Sung Joon Kim
• 金额: $ 44.87万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10291051
• 关键词: 2019-nCoV; Acetates; Alcohols; Anions; Antiviral Agents; Area; Biochemical Reaction; Biocompatible Materials; Biological Availability; Biomedical Research; COVID-19; Cations; Colorado; Competence; Complex; Coronavirus; Cosmetics; Data; Detergents; Disaccharides; Drug Delivery Systems; Drug Industry; Environment; Enzymes; Esterification; Esters; Ethers; Excipients; Fatty Acids; Food Industry; Glycolipids; Goals; Handwashing; Infection; Kinetics; Lead; Lipase; Liquid substance; Lubrication; Membrane; Mentors; Methodology; Mission; Missouri; Molecular Conformation; Oligonucleotides; Pharmaceutical Preparations; Pharmacologic Substance; Polysaccharides; Preparation; Process; Property; Public Health; Reaction; Research; Solvents; Structure; Students; Sugar Acids; Sugar Alcohols; System; Time; Training; United States National Institutes of Health; Universities; Unsaturated Fatty Acids; Vesicle; Viral; Water; Wichita; absorption; amphiphilicity; base; career; controlled release; design; enzyme activity; experience; experimental study; improved; innovation; molecular dynamics; pandemic disease; reduce symptoms; spectroscopic survey; sugar; surfactant; tool; undergraduate research experience; undergraduate student

Project Summary Fatty acid sugar esters are a type of nonionic glycolipid surfactants and can be made from renewable biomaterials (saccharides and fatty acids). These biosurfactants are non-toxic, tasteless, odorless, nonirritant, and biodegradable with broad applications in pharmaceuticals, detergents and cleaners, cosmetics, and the food industry. As a timely application, these biosurfactants could control the spread of coronavirus-2 (SARS- CoV-2) by disrupting viral membrane, serving as handwashing and cleaning agents, and targeting and relieving the symptoms after infection. Enzymatic synthesis can lead to regioselective biosurfactants, but is hampered by a lack of reaction systems that can dissolve both polar sugar molecules and non-polar fatty acids/fatty acid esters. The long-term goal is to mentor and guide a team of undergraduates to develop a general methodology for efficient synthesis of glycolipid-type biosurfactants. The main objective of this proposal is for students to synthesize functionalized ionic solvents, called ionic liquids (ILs), that are lipase- compatible and can dissolve sugars and fatty acids/fatty acid esters, and conduct enzymatic preparation of sugar fatty acid esters in ionic media. The central hypothesis is that ionic liquids can be functionalized to afford high substrate dissolution and high lipase activity at the same time to promote efficient synthesis of glycolipid-type biosurfactants. To achieve this objective, three Specific Aims are proposed: Specific Aim 1: Design “water-like” multifunctional ILs that can dissolve sugars and are compatible with lipases. Specific Aim 2: Synthesize mono- and disaccharide fatty acid esters via enzymatic (trans)esterifications in functionalized ionic solvents. Specific Aim 3: Prepare oligo- and polysaccharide fatty acid esters via enzymatic transesterification in functionalized ionic solvents. This research is innovative and significant because the synergistic combination of substrate-dissolving ILs and their high compatibility with enzymes will enable students to create a general methodology for enzymatic synthesis of biosurfactants. The primary impact of this project will be working with a predominantly undergraduate student research team to develop an efficient preparation of a variety of sugar-based biosurfactants that have broad applications in the pharmaceutical industry. The project will involve the significant participation of undergraduate students in all stages of the research, including implementation of research plans and analysis of findings. These research experiences will develop undergraduate student research competencies, thereby preparing them for careers in biomedical research and/or graduate studies, while additionally strengthening the research environment at the University of Northern Colorado. The main objective of this proposal is consistent with the NIH mission to develop efficient reaction systems to produce biosurfactants with major uses in pharmaceuticals and, particularly in controlling the spread of Covid-19 in the current pandemic, and AREA priorities to provide biomedical research experiences for undergraduates and enhance the institutional research environment.

项目摘要 脂肪酸糖酯是一类非离子糖脂表面活性剂，可由可再生的 生物材料（脂肪酸和脂肪酸）。这些生物表面活性剂无毒、无味、无嗅、无刺激性， 和可生物降解的，广泛应用于药物、洗涤剂和清洁剂、化妆品， 食品行业作为一个及时的应用，这些生物表面活性剂可以控制冠状病毒-2（SARS- CoV-2）通过破坏病毒膜，作为洗手和清洁剂，以及靶向和 减轻感染后的症状。酶促合成可产生区域选择性生物表面活性剂，但 由于缺乏既能溶解极性糖分子又能溶解非极性脂肪酸的反应体系， 酸/脂肪酸酯。长期目标是指导和指导一个本科生团队， 有效合成糖脂类生物表面活性剂的一般方法。的主要目标 一个建议是让学生合成功能化的离子溶剂，称为离子液体（IL），这是脂肪酶- 相容，并能溶解糖和脂肪酸/脂肪酸酯，并进行酶促制备， 糖脂肪酸酯在离子介质中。中心假设是离子液体可以被官能化以 同时提供高底物溶解和高脂肪酶活性，以促进高效合成 糖脂类生物表面活性剂。为实现这一目标，提出了三个具体目标：具体目标1： 设计“水状”多功能离子液体，可以溶解糖，并与脂肪酶相容。具体目标 2：在官能化的反应器中通过酶促（反式）酯化合成单糖和二糖脂肪酸酯 离子溶剂具体目标3：通过酶促反应制备寡糖和多糖脂肪酸酯 在官能化离子溶剂中的酯交换反应。本研究具有创新性和重要意义， 溶解底物IL及其与酶的高相容性的协同组合将使得 学生创建一个生物表面活性剂的酶促合成的一般方法。的主要影响 该项目将与一个以本科生为主的研究团队合作，开发一种有效的 制备各种糖基生物表面活性剂，在制药中具有广泛的应用 行业该项目将涉及本科生在所有阶段的重要参与， 研究，包括执行研究计划和分析研究结果。这些研究经验将 培养本科生的研究能力，从而为他们在生物医学领域的职业生涯做好准备 研究和/或研究生课程，同时加强大学的研究环境 位于北方科罗拉多。该提案的主要目标与NIH的使命一致，即开发 生产生物表面活性剂的有效反应系统，该生物表面活性剂主要用于药物，特别是 控制当前大流行中Covid-19的传播，以及区域优先提供生物医学研究 为本科生提供经验，并改善机构研究环境。