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.

项目概要 脂肪酸糖酯是一种非离子糖脂表面活性剂，可由可再生原料制成 生物材料（糖类和脂肪酸）。这些生物表面活性剂无毒、无味、无臭、无刺激性， 可生物降解，广泛应用于药品、洗涤剂和清洁剂、化妆品和 食品工业。如果及时应用，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，充当洗手剂和清洁剂，并靶向和 缓解感染后的症状。酶促合成可以产生区域选择性生物表面活性剂，但 由于缺乏可以溶解极性糖分子和非极性脂肪的反应系统而受到阻碍 酸/脂肪酸酯。长期目标是指导和指导本科生团队发展 有效合成糖脂型生物表面活性剂的一般方法。此举的主要目标 建议学生合成功能化离子溶剂，称为离子液体（IL），它们是脂肪酶 相容并能溶解糖和脂肪酸/脂肪酸酯，并进行酶法制备 离子介质中的糖脂肪酸酯。中心假设是离子液体可以功能化 同时提供高底物溶解度和高脂肪酶活性，促进高效合成 糖脂型生物表面活性剂。为了实现这一目标，提出了三个具体目标： 具体目标 1： 设计可溶解糖且与脂肪酶相容的“类水”多功能离子液体。具体目标 2：通过功能化酶促（反式）酯化合成单糖和二糖脂肪酸酯 离子溶剂。具体目标 3：通过酶法制备寡糖和多糖脂肪酸酯 功能化离子溶剂中的酯交换反应。这项研究具有创新性和意义，因为 底物溶解性 IL 的协同组合及其与酶的高度相容性将使 学生创建生物表面活性剂酶法合成的通用方法。主要影响 该项目将与一个以本科生为主的研究团队合作，开发一个高效的 制备多种在制药领域具有广泛应用的糖基生物表面活性剂 行业。该项目将涉及本科生在各个阶段的大量参与 研究，包括研究计划的实施和结果分析。这些研究经验将 培养本科生的研究能力，从而为他们从事生物医学职业做好准备 研究和/或研究生学习，同时进一步加强大学的研究环境 北科罗拉多州。该提案的主要目标与 NIH 的使命一致，即开发 高效的反应系统来生产生物表面活性剂，主要用于制药，特别是 控制 Covid-19 在当前大流行中的传播，AREA 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。