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·贝斯正在研究如何利用人类肠道微生物区系--生活在人类肠道中的数万亿细菌--来生产对社会重要的化学物质，用于工业过程。这类商品化学品通常来自化石燃料，这是一种不可再生的资源。一种更可持续的大宗化学品潜在原料是木质素。木质素是由植物制造的，是地球上最丰富和化学上最独特的聚合物之一。尽管木质素储量丰富，但缺乏将木质素转化为有用的商品化学品的有效方法。这项工作将检验这样一个假设，即人类的肠道是一个未被开发的细菌储存库，可以有效地将木质素转化为令人满意的化学物质。其基本原理是，木质素是食用植物的一种成分，肠道细菌只有几个小时的时间来分解通过肠道的膳食木质素。该项目有两个目标：(1)鉴定人体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。这项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研究。具体地说，将实施新的体验式学习计划，让高中生和本科生参与富含木质素的饮食干预，随后检查饮食对他们自己肠道微生物群的影响。通过与科学研究建立个人联系，这些项目的目标是提高学生的科学自我效能。由于现有方法要么受到低效的生物催化步骤的限制，要么受到产生产品混合物的化学方法的限制，因此需要使用生物和化学方法来解构木质素。该项目的总体目标是发现新的细菌，将木质素转化为增值产品，并开发可能用于在任何生物系统中发现此类生物催化剂的可靠工具。为了实现该项目的目标，将使用生物正交非规范氨基酸标签(BONCAT)方法来识别能够分解木质素的特定肠道细菌。将开发木质素涂层磁珠，将木质素降解的候选细菌从肠道复杂的细菌群落中分离出来。将使用2D核磁共振波谱来表征人类肠道细菌如何改变木质素聚合物，并将实施同位素跟踪代谢组学来识别结果的化学产品。发现有效地将木质素分解为木质素的新方法，通过开辟新的增值和生物可再生途径来构建关键的化学构建块，有可能对可持续化学有用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.