CAREER: A multidisciplinary approach to the investigation of secondary metabolism in nematodes

职业：研究线虫次生代谢的多学科方法

• 批准号: 1555050
• 负责人: Rebecca Butcher
• 金额: $ 72.2万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1555050&HistoricalAwards=false
• 关键词: CAREER; multidisciplinary; approach; investigation; secondary

With this award, funded by the Chemistry of Life Processes Program in the Chemistry Division, Dr. Rebecca A. Butcher of the University of Florida is investigating the chemical signals used by different species of nematodes (roundworms) to control their development. Nematodes are very diverse (over 25,000 characterized species) and can be parasitic, causing widespread disease in plants and animals (including humans). Despite the huge impact of nematodes, surprisingly little is known about chemical signaling in members of this important class of organisms. Investigations into the chemical structures and biosynthesis of the chemical signals used by nematodes should enable the development of new chemical tools and strategies to interfere with their life cycles and survival and thus provide new treatment options. This award also promotes the development a discovery-based laboratory course for undergraduates in the isolation of natural products from microorganisms that live inside plants. In this course, students isolate endophytes from plants, generate extracts from these endophytes, and screen the extracts for anti-nematode activities. This award aims to characterize the chemical structures of key small-molecule signals that nematodes use to control their development. The small-molecule signals from representative nematode species can be identified using comparative metabolomics between wild-type worms and biosynthetic mutants. The relevant compounds are then be purified using mass-guided fractionation, and their structures characterized using NMR spectroscopy. Comparison of the chemical structures and biosynthetic gene sequences from different nematode species enables the roles of specific enzymatic domains to be mapped across nematode evolution. To study the activities of specific enzymatic domains, this study uses a multidisciplinary approach incorporating tools from biochemistry, organic chemistry, structural biology, analytical chemistry, and nematode genetics. The results of this award are expected to shed light on how nematodes control their life cycles and the development of novel methods to reduce the survival of parasitic nematodes. The educational portion of this project increases retention of undergraduate students in science fields by developing a discovery-based (rather than cookbook style) laboratory course in natural product identification. The proposed course extends the research opportunities for undergraduate and high school students and may lead to the discovery of novel bacterial/fungal metabolites with anti-nematode activities.

佛罗里达大学的丽贝卡·A·布彻 (Rebecca A. Butcher) 博士获得了化学部生命过程化学项目的资助，正在研究不同种类的线虫（蛔虫）用于控制其发育的化学信号。 线虫种类繁多（超过 25,000 种特征性物种），并且可以寄生，在植物和动物（包括人类）中引起广泛的疾病。尽管线虫影响巨大，但令人惊讶的是，人们对这一重要生物体成员的化学信号知之甚少。对线虫使用的化学信号的化学结构和生物合成的研究应该能够开发新的化学工具和策略来干扰其生命周期和生存，从而提供新的治疗选择。该奖项还促进了本科生从植物体内微生物中分离天然产物的基于发现的实验室课程的开发。在本课程中，学生从植物中分离内生菌，从这些内生菌中产生提取物，并筛选提取物的抗线虫活性。 该奖项旨在表征线虫用来控制其发育的关键小分子信号的化学结构。 可以使用野生型线虫和生物合成突变体之间的比较代谢组学来鉴定来自代表性线虫物种的小分子信号。 然后使用质量引导分馏纯化相关化合物，并使用核磁共振波谱表征其结构。通过比较不同线虫物种的化学结构和生物合成基因序列，可以绘制线虫进化过程中特定酶结构域的作用。 为了研究特定酶域的活性，本研究采用多学科方法，结合了生物化学、有机化学、结构生物学、分析化学和线虫遗传学的工具。 该奖项的结果预计将揭示线虫如何控制其生命周期以及开发减少寄生线虫存活的新方法。 该项目的教育部分通过开发基于发现（而不是食谱风格）的天然产品鉴定实验室课程来提高本科生在科学领域的保留率。拟议的课程扩大了本科生和高中生的研究机会，并可能导致发现具有抗线虫活性的新型细菌/真菌代谢物。

项目成果

Acyl-CoA Oxidases Fine-Tune the Production of Ascaroside Pheromones with Specific Side Chain Lengths

• DOI: 10.1021/acschembio.7b01021
• 发表时间: 2018-04-01
• 期刊: ACS CHEMICAL BIOLOGY
• 影响因子: 4
• 作者: Zhang, Xinxing;Wang, Yuting;Butcher, Rebecca A.
• 通讯作者: Butcher, Rebecca A.

Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans

• DOI: 10.1073/pnas.1608262113
• 发表时间: 2016-09-06
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Zhang, Xinxing;Li, Kunhua;Butcher, Rebecca A.
• 通讯作者: Butcher, Rebecca A.