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

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。新墨西哥大学(UNM)是一所为拉美裔服务的机构，其本科生中有50%是拉美裔或拉丁裔，也是一所少数族裔占多数的机构，其本科生中59%的人认同代表不足的群体。UNM和NSF遗传编码材料中心(C-GEM)之间的化学研究和教育伙伴关系旨在增加化学专业小规模本科生的留校率。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，并加强他们作为化学家的认同感。这些活动将为他们进入研究生院或化学职业生涯做准备。这项研究将集中在设计一种相对容易操作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用来生产这些化学物质的机械。通过这些研究，该项目致力于开发一种路线，以改变和测试用于制造这些增值产品的路线，对于通往关键分子或材料目标的混合合成/生物催化路线具有潜在的长期影响。该项目旨在开发两种协同方法来研究和利用生产核糖体合成和翻译后修饰多肽(RIPP)类天然产物所涉及的生物合成机制，长期目标是产生大量的天然产物类化合物，可以筛选出新的有用的性质和活性。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的灵活异源宿主。在目标2中，将开发一个计算工作流程，利用两阶段多尺度分子动力学模拟来模拟RIPP前体多肽在生物合成酶活性部位的行为，以更深入地了解这些酶的功能并指导工程工作。该项目将为每年6名学生提供资金，让他们在本科生涯早期参加C-GEMS夏季本科生研究项目，为他们提供在合作和支持的环境中的第一次研究经验，并加强他们作为科学家的身份认同。它还将资助四名本科生在新墨西哥州大学开展研究，并在以小规模学生为重点的科学会议上介绍他们的研究成果。这个项目得到了数学和物理科学局化学部和生物科学局分子和细胞生物科学部遗传机制组的部分支持。这个奖项反映了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，被认为是值得支持的。

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.