CAREER: The Human Gut as an Untapped Reservoir for Bacteria and Enzymes that Degrade Lignin, a Potential Sustainable Source for Critical Chemicals

职业：人类肠道是降解木质素的细菌和酶的未开发储库，木质素是关键化学品的潜在可持续来源

• 批准号: 2339225
• 负责人: Elizabeth Bess
• 金额: $ 66.36万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-04-01 至 2029-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2339225&HistoricalAwards=false
• 关键词: CAREER; Human; Gut; Untapped; Reservoir

With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, Elizabeth Bess from the University of California, Irvine, is studying how the human gut microbiota—trillions of bacteria that live in the intestines of human beings—can be leveraged to produce chemicals that are important to society for industrial processes. Such commodity chemicals are typically sourced from fossil fuels, a non-renewable resource. A more sustainable potential feedstock for commodity chemicals is lignin. Lignin is made by plants and is one of Earth’s most abundant and chemically unique polymers. Despite its abundance, efficient methods to convert lignin into useful commodity chemicals are lacking. The work will test the hypothesis that the human gut is an untapped reservoir of bacteria that could efficiently convert lignin into desirable chemicals. The rationale is that lignin is a component of dietary plants, and intestinal bacteria only have hours to deconstruct dietary lignin as it transits the intestines. The project has two aims: (1) identify bacterial species in the human gut that deconstruct lignin and (2) reveal the chemical products of this process. This research project offers an opportunity to engage students from underrepresented groups in scientific inquiry. Specifically, new experiential-learning programs will be implemented in which high school and undergraduate students participate in a lignin-rich diet intervention and subsequently examine the impact of diet on their own gut microbiota. By establishing a personal connection to scientific research, these programs have the goal of enhancing students science self-efficacy.Biological and chemical approaches to deconstruct lignin are needed as existing approaches are limited either by inefficient biocatalytic steps and/or by chemical methods that yield product mixtures and thus require costly purification. The overall objective of this project is to uncover new bacteria to convert lignin to value-added products and to develop reliable tools that could potentially be used to discover such biocatalysts in any biological system. To achieve the goals of this project, a bio-orthogonal noncanonical amino acid tagging (BONCAT) method will be used to identify specific gut bacteria that deconstruct lignin. Lignin-coated magnetic beads will be developed to separate bacterial candidates for lignin degradation from the complex bacterial communities of the gut. Characterization of how human gut bacteria alter the lignin polymer will be performed using 2D nuclear magnetic resonance spectroscopy, and isotope-tracing metabolomics will be implemented to identify the chemical products that result. Discovery of new ways to efficiently deconstruct lignin to lignin has the potential to be useful for sustainable chemistryby opening up new value-added and biorenewable pathways to key chemical building blocks.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学过程中的化学过程（CLP）方案的支持下，来自加利福尼亚大学欧文分校的伊丽莎白·贝丝（Elizabeth Bess）正在研究如何使用人类肠道菌群（千千种细菌）生活，这些细菌生活在人类的肠道中，可以利用对工业过程的社会而生产的化学物质。这种商品化学品通常来自化石燃料，这是一种不可再生的资源。木质素是商品化学品的更可持续的潜在原料。木质素是由植物制成的，是地球最丰富，最独特的聚合物之一。尽管它丰富了，但仍缺乏将木质素转化为有用的商品化学物质的有效方法。这项工作将检验人类肠道是未开发的细菌储层的假设，可以有效地将木质素转化为理想的化学物质。理由是木质素是饮食植物的组成部分，肠道细菌只有小时来解构饮食木质素，因为它可以转移肠道。该项目有两个目的：（1）鉴定人类肠道中的细菌种类，使木质素解构木质素和（2）揭示了该过程的化学产物。该研究项目提供了一个机会，可以让来自代表性不足小组的学生参与科学探究。具体而言，将实施新的经验丰富的学习计划，其中高中和本科生参加了富含木质素的饮食干预措施，并随后研究饮食对自己的肠道微生物群的影响。通过与科学研究建立个人联系，这些计划的目的是增强学生的科学自我有效性。需要解构木质素的生物学和化学方法，因为现有方法受到无效的生物催化步骤和/或通过产生产品混合物的化学方法的限制，因此需要成本昂贵。该项目的总体目的是发现新的细菌将木质素转化为增值产品，并开发可靠的工具，这些工具有可能被用于在任何生物系统中发现此类生物催化剂。为了实现该项目的目标，将使用生物正交非氨基酸标记（Boncat）方法来识别解构木质素的特定肠道细菌。将开发木质素涂层的磁珠来将候选细菌降解与肠道复杂细菌群落分离。将使用2D核磁共振光谱法进行木质素聚合物如何改变木质素聚合物的表征，并将实现对同位素追踪代谢组学的实施，以识别产生的化学产品。发现有效解构木质素对木质素的新方法有可能对可持续的化学有用，从而开放新的增值和生物可生产途径，可通往关键的化学基础。该奖项反映了NSF的法定任务，并通过使用该基金会的知识分子和更广泛的影响来评估NSF的法定任务。