PREC Track 1: Expanding the Chemical Space of Ribosomally Synthesized and Post-Translationally Modified peptides

PREC 轨道 1：扩展核糖体合成和翻译后修饰肽的化学空间

• 批准号: 2216836
• 负责人: Mark Walker
• 金额: $ 86.86万
• 依托单位: University of New Mexico
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2216836&HistoricalAwards=false
• 关键词: PREC; Track; Expanding; Chemical; Space

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). The University of New Mexico (UNM) is a Hispanic-Serving Institution with 50% of its undergraduate student body identifying as Hispanic or Latino, and a majority-minority institution with 59% of its undergraduate student body identifying with an underrepresented group. This Partnership for Research and Education in Chemistry between UNM and the NSF Center for Genetically Encoded Materials (C-GEM) aims to increase the retention of minoritized undergraduate students in chemistry. It will focus on providing mentoring and research experiences to undergraduates to increase their sense of belonging in chemistry and strengthen their identity as chemists. These activities will prepare them for graduate school or careers in chemistry. The research will focus on engineering a relatively easily manipulable bacterium to produce chemical products of value, and using computational methods to study the machinery these bacteria use to produce these chemicals. Through these studies, this project endeavors to develop a route to alter and test the pathways used to make these value-added products, for potential long term implications for hybrid synthetic/biocatalytic routes to key molecular or materials targets. This project aims to develop two synergistic approaches to study and utilize biosynthetic machinery involved in the production of ribosomally synthesized and post-translationally modified peptide (RiPP) class of natural products, with the long-term goal of generating large libraries of natural product-like compounds that can be screened for new and useful properties and activities. In objective 1, Bacillus subtilis, a Gram-positive bacterium for which wide array of genetic tools are available, will be developed as a flexible heterologous host for the production of RiPPs. In objective 2, a computational workflow utilizing two-stage multiscale molecular dynamics simulations to model the behavior of the RiPP precursor peptide in the active sites of the biosynthetic enzymes will be developed to gain a deeper understanding of how these enzymes function and to guide engineering efforts. This project will provide funding for six students annually to take part in C-GEMs summer undergraduate research program early in their undergraduate career, providing them with their first research experience in a collaborative and supportive environment, and strengthening their identity as scientists. It will also provide funding for four undergraduate students to perform research at UNM and present their research at scientific conferences focused on minoritized students. This project is partially supported by the Chemistry Division of the Mathematical and Physical Sciences Directorate and by the Genetic Mechanisms Cluster of the Molecular and Cellular Biosciences Division of the Biological Sciences Directorate.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.

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。新墨西哥大学（UNM）是一所为西班牙裔服务的大学，50%的本科生是西班牙裔或拉丁裔，也是一所占多数的少数民族大学，59%的本科生属于代表性不足的群体。新墨西哥大学和美国国家科学基金会遗传编码材料中心（C-GEM）之间的化学研究和教育合作伙伴关系旨在增加化学专业少数民族本科生的保留率。它将侧重于为本科生提供指导和研究经验，以增加他们对化学的归属感，加强他们作为化学家的身份。这些活动将为他们进入研究生院或从事化学工作做准备。这项研究将集中于设计一种相对容易操纵的细菌来生产有价值的化学产品，并使用计算方法来研究这些细菌生产这些化学物质的机制。通过这些研究，该项目努力开发一种途径来改变和测试用于制造这些增值产品的途径，以潜在的长期影响混合合成/生物催化途径到关键分子或材料目标。该项目旨在开发两种协同方法来研究和利用涉及核糖体合成和翻译后修饰肽（RiPP）类天然产物生产的生物合成机制，其长期目标是产生大型天然产物样化合物文库，可以筛选新的有用的特性和活性。在目标1中，枯草芽孢杆菌是一种革兰氏阳性细菌，具有广泛的遗传工具，将被开发为生产RiPPs的灵活的异源宿主。在目标2中，利用两阶段多尺度分子动力学模拟来模拟RiPP前体肽在生物合成酶活性位点的行为的计算工作流将被开发出来，以更深入地了解这些酶的功能并指导工程工作。该项目每年将资助六名学生在本科生涯早期参加C-GEMs暑期本科生研究项目，为他们提供在协作和支持环境中的第一次研究经验，并加强他们作为科学家的身份。它还将为四名本科生提供资金，让他们在新墨西哥大学进行研究，并在以少数族裔学生为重点的科学会议上展示他们的研究成果。该项目得到数学和物理科学理事会化学司和生物科学理事会分子和细胞生物科学司遗传机制组的部分支持。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。