Collaborative Research: How bacteria control manganese(IV) oxide biomineralization using a multicopper oxidase complex

合作研究：细菌如何使用多铜氧化酶复合物控制氧化锰（IV）生物矿化

• 批准号: 1807222
• 负责人: Thomas Spiro
• 金额: $ 27.3万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807222&HistoricalAwards=false
• 关键词: Collaborative; Research; How; bacteria; control

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Bradley Tebo from Oregon Health & Science University and Dr. Thomas Spiro from the University of Washington to find out how bacteria change dissolved manganese (Mn) into manganese oxide minerals. This chemical process produces manganese oxides that are widespread, highly reactive, efficient catalysts that play important roles in elemental biogeochemical cycles. Although these oxides are primarily made by microbial processes, the biological means for their formation are poorly understood. This project reveals the pathway of bacterial manganese oxide production, using the first purified active manganese-oxidizing enzyme complex. The project may uncover the biochemistry of how two processes-manganese oxidation and mineral formation-are achieved, laying the foundation for future application of biologically-derived manganese oxides in clean water technologies and energy storage and production. This project enhances the training of the next generation of scientists in interdisciplinary methods, and serves as a vehicle in outreach programs to engage undergraduate, middle, and high school students in studies of microbiology and biochemistry, as related to environmental science. In addition, postdoctoral fellows develop a Saturday Academy course targeting either 6-8 or 9-12 grade students and focusing on the importance of microbiology and biochemistry as related to environmental science. The Saturday Academy provides professional development for the postdoctoral fellow as the instructor.The project represents an investigation of how a purified protein can accomplish the difficult two-electron oxidation of Mn(II), forming a nanoparticulate MnO2 mineral product. Results to date indicate that the active protein belongs to the well-known multicopper oxidase family of enzymes, but with a unique ability to adapt the polynuclear chemistry of manganese to perform the catalysis. The research efforts are focused on establishing a molecular-level detailed mechanism of the catalysis, by resolving manganese oxidation intermediates and studying the effects of key mutations with an array of spectroscopic techniques. The spectroscopic studies are complemented by modeling, crystallography, and cryo-electron microscopy work to derive the 3D atomic structure of the enzyme. In the context of broader environmental applicability, the research explores the effect of other metals occurring in the environment on the enzymatic catalysis of manganese oxidation.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.

通过该奖项，化学生命过程的化学过程计划将资助俄勒冈健康与科学大学的Bradley Tebo博士，以及华盛顿大学的Thomas Spiro博士，以了解细菌如何改变溶解的锰（MN）为锰氧化物矿物质。这种化学过程产生的锰氧化物是广泛，高反应性，高效的催化剂，它们在元素生物地球化学周期中起重要作用。尽管这些氧化物主要是由微生物过程制成的，但其形成的生物学手段知之甚少。该项目使用首次纯化的活性锰氧化酶复合物揭示了细菌氧化物产生的途径。该项目可能会揭示生物化学如何实现两种过程 - 山加氧化和矿物质形成，为将来在清洁水技术以及能量储能和生产中生产生物学衍生的锰氧化物奠定了基础。该项目增强了对下一代科学家在跨学科方法的培训，并用作外展计划的工具，以吸引本科，中学和高中生从事微生物学和生物化学研究，与环境科学有关。 此外，博士后研究员开发了一个针对6-8或9-12年级学生的星期六学院课程，并专注于与环境科学相关的微生物学和生物化学的重要性。周六学院为博士后研究员提供了专业发展，该项目代表了对纯化蛋白如何完成MN（II）的困难的两电子氧化的调查，形成了纳米含量的MNO2矿物产品。迄今为止的结果表明，活性蛋白属于酶的多杆氧化酶家族，但具有独特的能力，可以使锰的多核化学能够进行催化。研究工作的重点是通过解决锰氧化中间体并使用一系列光谱技术来建立催化的分子级详细机制。光谱研究通过建模，晶体学和冷冻电子显微镜工作来补充，以得出酶的3D原子结构。在更广泛的环境适用性的背景下，该研究探讨了在环境中发生的其他金属对锰氧化的酶促催化的影响。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优点和更广泛影响的审查标准来评估的。

项目成果

Metallo-inhibition of Mnx, a bacterial manganese multicopper oxidase complex

Mnx（一种细菌锰多铜氧化酶复合物）的金属抑制

• DOI: 10.1016/j.jinorgbio.2021.111547
• 发表时间: 2021
• 期刊: Journal of Inorganic Biochemistry
• 影响因子: 3.9
• 作者: Soldatova, Alexandra V.;Fu, Wen;Romano, Christine A.;Tao, Lizhi;Casey, William H.;Britt, R. David;Tebo, Bradley M.;Spiro, Thomas G.
• 通讯作者: Spiro, Thomas G.