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

在化学系生命过程化学（CLP）项目的支持下，来自加州大学欧文分校的伊丽莎白·贝斯（Elizabeth Bess）正在研究如何利用人类肠道微生物——生活在人类肠道中的数万亿细菌——来生产对社会工业过程至关重要的化学物质。这些商品化学品通常来自化石燃料，这是一种不可再生的资源。一种更具可持续性的潜在原料是木质素。木质素是由植物制造的，是地球上最丰富、化学性质最独特的聚合物之一。尽管木质素丰富，但缺乏将木质素转化为有用的商品化学品的有效方法。这项工作将验证一个假设，即人类肠道是一个未开发的细菌储存库，可以有效地将木质素转化为理想的化学物质。其基本原理是木质素是膳食植物的一种成分，而肠道细菌只有几个小时的时间来分解膳食木质素，因为它通过肠道。该项目有两个目的：(1)确定人类肠道中分解木质素的细菌种类；(2)揭示这一过程的化学产物。这个研究项目提供了一个机会，让来自代表性不足群体的学生参与科学探究。具体而言，将实施新的体验式学习计划，其中高中生和本科生参与富含木质素的饮食干预，随后检查饮食对其自身肠道微生物群的影响。通过建立个人与科学研究的联系，这些项目的目标是提高学生的科学自我效能感。由于现有的方法受到低效的生物催化步骤和/或产生产物混合物的化学方法的限制，因此需要生物和化学方法来解构木质素，因此需要昂贵的净化。该项目的总体目标是发现将木质素转化为增值产品的新细菌，并开发可用于在任何生物系统中发现此类生物催化剂的可靠工具。为了实现这个项目的目标，一种生物正交非规范氨基酸标记（BONCAT）方法将被用来识别分解木质素的特定肠道细菌。木质素包覆磁珠将被开发用于从肠道复杂的细菌群落中分离木质素降解的候选细菌。人类肠道细菌如何改变木质素聚合物的特性将使用二维核磁共振波谱进行，并将实施同位素示踪代谢组学来确定由此产生的化学产物。发现有效地将木质素分解为木质素的新方法，通过为关键化学构件开辟新的增值和生物可再生途径，有可能对可持续化学有用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.