Enzymatic Synthesis of Sugar-Derived Biosurfactants Using Multifunctional Ionic Liquids

项目摘要 脂肪酸糖酯是一种非离子糖脂表面活性剂，可以由可再生的 生物材料(糖和脂肪酸)。这些生物表面活性剂无毒、无味、无臭、无刺激性， 和生物可降解性，在制药、洗涤剂和清洁剂、化妆品和 食品工业。作为及时的应用，这些生物表面活性剂可以控制冠状病毒-2(SARS-2)的传播。 CoV-2)通过破坏病毒膜、用作洗手和清洁剂以及靶向和 缓解感染后的症状。酶法合成可以产生区域选择性的生物表面活性剂，但 由于缺乏能同时分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一支本科生团队发展一种 高效合成糖脂类生物表面活性剂的通用方法学。这项工作的主要目标是 学生的建议是合成功能化的离子溶剂，称为离子液体(ILS)，即脂肪酶- 相容并能溶解糖和脂肪酸/脂肪酸酯，并进行酶法制备 离子介质中的蔗糖脂肪酸酯。中心假设是离子液体可以被功能化以 提供高底物溶解度和高脂肪酶活性的同时，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： 设计一种能溶解糖分并与脂肪酶相容的“水状”多功能ILS。特定目标 2：通过官能化的酶(反式)酯化反应合成单糖和双糖脂肪酸酯 离子溶剂。具体目标3：酶法制备寡糖和多糖酯 功能化离子溶剂中的酯交换反应。这项研究具有创新性和重要意义，因为 底物溶解离子液体的协同组合及其与酶的高度兼容性将使 学生创建一种酶法合成生物表面活性剂的通用方法。其主要影响是 该项目将与一个以本科生为主的研究团队合作，以开发一种高效的 多种糖基生物表面活性剂的制备及其在医药中的广泛应用 工业。该项目将使本科生大量参与到课程的各个阶段 研究，包括实施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/或研究生学习，同时进一步加强大学的研究环境 位于北科罗拉多州。这项提案的主要目标与美国国立卫生研究院的任务一致，即开发 生产生物表面活性剂的高效反应系统，主要用于制药，特别是在 在当前的大流行中控制新冠肺炎的传播，以及提供生物医学研究的优先领域 为本科生提供经验，优化院校研究环境。

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.