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源。然而，这种营养源只有一小部分微生物才能从生物学角度获取，这些微生物可以将其还原为铵 NH4+。生物固氮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。负责该反应的酶是固氮酶，其活性依赖于其相关的金属辅因子。该项目旨在阐明涉及由蛋白质 NifU 和 NifS 促进的固氮酶金属辅因子合成的初始反应步骤。先前的研究已经确定这些蛋白质参与支持固氮酶金属辅因子的初始铁硫 (Fe-S) 结构单元的合成。该奖项支持的研究将探索 NifU 和 NifS 如何在模型细菌 Azotobacter vinelandii 中组装这些 Fe-S 单元。这个跨学科的国际合作项目将通过研究经验和专业发展机会吸引本科生和研究生。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) 为研究生提供海外合作研究经验；(b) 为当地本科生提供指导研究奖学金。这些努力对于为多元化和全球化的劳动力队伍培养下一代 STEM 领导者具有重要意义。该项目旨在通过确定 1) 与 NifU 相关的新型簇物种的位置和光谱特征，2) 在自然环境和生理还原剂存在的情况下研究 Fe-S 簇合成的机理和化学步骤。该过程中涉及其他因素，以及3）新鉴定的簇物种作为固氮酶金属簇合成的构建块的反应性。揭示固氮的分子和机制细节对于理解其在整个进化过程中持续和保守的需求具有内在的智力价值。这些原理还可以指导在更复杂的系统上对 Fe-S 簇进行基础研究，这些系统利用参与其他细胞过程的金属辅因子。这个美国/德国合作项目得到了美国国家科学基金会（化学、分子和细胞生物科学部门联合）和德国研究基金会（DFG）的支持。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准。