NSF/BIO-DFG: Biological Fe-S intermediates in the synthesis of nitrogenase metalloclusters

NSF/BIO-DFG：固氮酶金属簇合成中的生物 Fe-S 中间体

• 批准号: 2335999
• 负责人: Patricia Dos Santos
• 金额: $ 54.82万
• 依托单位: Wake Forest University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2335999&HistoricalAwards=false
• 关键词: NSF; BIO; DFG; Biological; Fe

Nitrogen gas (N2) is the most abundant source of nitrogen on Earth. However, this nutrient source is only biologically accessible to a subset of microbes that can reduce it into ammonium NH4+. The biological capacity to fix N2 is a critical step in the biogeochemical nitrogen cycle and essential to life on Earth. The enzyme responsible for this reaction is nitrogenase and its activity relies on its associated metallocofactors. This project aims to elucidate initial reaction steps involving the synthesis of nitrogenase metallocofactors that are promoted by proteins NifU and NifS. Previous studies have established the involvement of these proteins in supporting the synthesis of initial iron-sulfur (Fe-S) building blocks for nitrogenase metallocofactors. The research supported by this award will explore how NifU and NifS assemble these Fe-S units in the model bacterium Azotobacter vinelandii. The interdisciplinary, collaborative international project will engage undergraduate and graduate students through research experiences and professional development opportunities. A German and an American PI partnership will support two synergistic research and professional development efforts: (a) collaborative research experiences abroad for graduate students and (b) mentored research fellowships for local undergraduate students. These efforts are relevant for preparing the next generation of STEM leaders for a diverse and globalized workforce. The project is aimed at investigating the mechanistic and chemical steps of Fe-S cluster synthesis in the context of a native environment and the presence of physiological reductants by establishing 1) the location and spectroscopic features of novel cluster species associated with NifU, 2) the involvement additional factors in this process, and 3) the reactivity of newly identified cluster species as building blocks for the synthesis of nitrogenase metalloclusters. Uncovering molecular and mechanistic details that enable nitrogen fixation has intrinsic intellectual merit in understanding their sustained and conserved requirement throughout evolution. These principles can also guide foundational studies on Fe-S clusters on more complex systems that utilize metallocofactors participating in other cellular processes. This collaborative US/Germany project is supported by the US National Science Foundation (Chemistry and Molecular and Cellular Biosciences Divisions jointly) and the German Research Foundation (DFG).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.

氮气（N2）是地球上最丰富的氮来源。但是，这种营养源仅在生物学上可以访问一个可以将其降低到NH4+铵中的微生物的子集。固定N2的生物学能力是生物地球化学氮循环的关键步骤，对地球生命至关重要。负责该反应的酶是氮酶，其活性依赖于其相关的金属生产者。该项目旨在阐明涉及由NIFU和NIFS促进的氮酶金属合体的合成的初始反应步骤。先前的研究已经确定了这些蛋白质参与支持氮酶金属糖活性酶的初始铁硫（FE-S）构建基块的合成。该奖项支持的研究将探讨NIFU和NIFS如何在模型细菌Azotobacter Vinelandii中组装这些Fe-S单元。跨学科的协作国际项目将通过研究经验和专业发展机会与本科生和研究生。德国和美国的PI合作伙伴关系将支持两项协同研究和专业发展工作：（a）在国外为研究生提供的协作研究经验，以及（b）为当地本科生提供的研究研究奖学金。这些努力与准备下一代STEM领导者为多样化和全球化的劳动力做准备。该项目的目的是通过建立天然环境的背景下的Fe-S簇合成的机械和化学步骤来研究生理还原因子的存在。揭示能够固定氮的分子和机械细节具有内在的智力优点，可以理解它们在整个进化过程中的持续和保守要求。这些原理还可以指导有关利用参与其他细胞过程的金属生产者的更复杂系统的Fe-S簇的基础研究。该协作的美国/德国项目得到了美国国家科学基金会（共同的化学，分子和蜂窝生物科学部门）和德国研究基金会（DFG）的支持。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子和更广泛影响的评估审查审查标准来通过评估来通过评估来支持的。