CAREER: Mechanistic Studies of Phosphonate Biosynthesis and Degradation

这一无机化学、生物无机化学和金属有机化学项目的职业奖支持波士顿大学刘平华教授研究磷酸盐(含C-P键化合物)的生物合成和生物降解。磷酸盐广泛存在于自然界中，许多具有生物功能。此外，由于人造磷酸盐(如杀虫剂、农用杀虫剂)的广泛使用以及C-P键的极端惰性，磷酸盐在环境中积累，是土地和水污染的主要来源。到目前为止，只有一种特征性的C-P键形成酶，即磷酸烯醇式丙酮酸异构酶。本项目要研究的酶BCPD是第二种能够催化C-P键形成的酶。具体地说，两个辅因子--铁-硫簇和钴胺的作用正在研究中。拟议工作的第一部分中的这些机理研究将使设计磷酸盐谱分析(细胞中磷酸盐类的身份和浓度)的方法成为可能。这项工作的后半部分将确定细菌中导致磷酸盐降解的基因，这最终将使绿色化学家的开发能够利用生物工程来降解污染物。这项研究纳入了国际生物科学研究所的教育活动，旨在解决培养下一代生物科学家的重大问题，特别是：1)他们需要从全球的角度看待社会面临的技术挑战，例如环境保护；2)为高中生和本科生早期参与科学创造机会；3)需要对科学家进行跨学科培训，使他们能够更好地应对21世纪的化学、生物和技术挑战。

This CAREER award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Pinghua Liu at Boston University to study the biosynthesis and biodegradation of phosphonates (C-P bond containing compounds). Phosphonates exist widely in nature and many have biological functions. In addition, because of the wide use of man-made phosphonates (e.g., pesticides, agricultural insecticides) and the extremely inert nature of the C-P bond, phosphonates have accumulated in the environment and are a major source of both land and water pollution. To date, there is only one characterized C-P bond formation enzyme, phosphoenolpyruvate isomerase. The enzyme to be studied in this project, BcpD, is the second enzyme capable of catalyzing the C-P bond formation. Specifically, the roles of two cofactors, the iron-sulfur cluster and cobalamin are being investigated. These mechanistic studies in the first part of the proposed effort will enable the design of methods for phosphonate profiling (identities and concentration of phosphonates in a cell). The second half of the work will identify genes responsible for phosphonate degradation in bacteria, which will eventually allow the development of green chemistr to degrade pollutants using bioengineering. The research is integrated into the PI's educational activities, which aim at addressing significant issues in the training of the next generation of bioscientists, specifically: 1) their need to acquire a global perspective of the technical challenges faced by society, e.g., environmental protection; 2) the creation of opportunities for the early participation of high school and undergraduate students in the sciences; and 3) the need for the interdisciplinary training of scientists to better equip them to address the 21st century's chemical, biological, and technological challenges.