Mechanism and Role of Enzymatic P-Methyl Transfer

酶促 P-甲基转移的机制和作用

• 批准号: 1763237
• 负责人: Susan Wang
• 金额: $ 32.78万
• 依托单位: Case Western Reserve University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1763237&HistoricalAwards=false
• 关键词: Mechanism; Role; Enzymatic; Methyl; Transfer

With this award, the Chemistry of Life Processes Program in the Division of Chemistry is funding Dr. Susan Wang at Washington State University to characterize the unusual chemistry used by two enzymes that methylate phosphorus atoms: the "P-methyltransferases", PhpK and SD 1168. Compounds containing bonds between carbon and phosphorus (C-P) play important roles in agriculture, industry, and medicine. The C-P bond is resistant to being broken by water, making compounds that contain this stable structural feature commercially useful. In addition, it has been suggested that C-P formation may provide a mechanism for marine organisms to store, preserve, and cycle phosphorus. This project will investigate the physiological roles of the only known enzymes that form carbon-phosphorus-carbon (C-P-C) linkages, the "P-methyltransferases." Undergraduate and graduate students will receive broad multidisciplinary training in chemistry and biology. These trainees will also participate in an outreach program introducing rural and/or low-income preschool children to the life sciences as a potential career path.The focus here will be on two"P-methyltransferase enzymes, PhpK and SD 1168, that methylate phosphorus atoms. Both enzymes are capable of producing precursors for the important natural product phosphinothricin, a broad-spectrum herbicide with antibiotic properties. Both PhpK and SD 1168 are believed to utilize a combination of vitamin B12 and free radical chemistry to form C-P-C bonding sequences. SD 1168, from the marine bacterium Shewanella denitrificans, exhibits broader substrate specificity than PhpK. While its true biological function remains unknown, SD 1168 is a potential candidate for future engineering efforts to produce new C-P-C compounds. A multifaceted, collaborative approach combining spectroscopic, synthetic, molecular biology, microbiology, and crystallographic techniques will be used to determine the enzymatic mechanism for P-methylation and to pinpoint the physiological role of SD 1168 in its host organism. The results of the proposed research will provide insight into unusual, difficult chemistry and have implications for the biosynthesis of C-P natural products and related compounds.

有了这个奖项，化学系的生命过程化学项目正在资助华盛顿州立大学的Susan Wang博士，以表征两种甲基化磷原子的酶所使用的不寻常的化学：“P-甲基转移酶”，PhpK和SD 1168。 含碳磷化合物在农业、工业和医药等领域发挥着重要作用。 C-P键能抵抗水的破坏，使含有这种稳定结构特征的化合物在商业上有用。 此外，有人认为，C-P的形成可能为海洋生物储存，保存和循环磷提供了一种机制。 本计画将探讨唯一已知能形成碳-磷-碳（C-P-C）键的酵素--P-甲基转移酶的生理作用。“本科生和研究生将接受化学和生物学方面的广泛的多学科培训。 这些学员还将参加一项推广计划，向农村和/或低收入学龄前儿童介绍生命科学，作为潜在的职业道路。这里的重点将是两种“P-甲基转移酶，PhpK和SD 1168，使磷原子甲基化。这两种酶都能够产生重要的天然产物膦丝菌素（一种具有抗生素特性的广谱除草剂）的前体。 PhpK和SD 1168都被认为利用维生素B12和自由基化学的组合来形成C-P-C键合序列。 SD 1168，来自海洋细菌Shewanella plasticans，表现出比PhpK更广泛的底物特异性。 虽然SD 1168的真正生物学功能尚不清楚，但它是未来工程努力生产新C-P-C化合物的潜在候选物。 一个多方面的，合作的方法相结合的光谱，合成，分子生物学，微生物学和晶体学技术将被用来确定P-甲基化的酶机制，并查明SD 1168在其宿主生物体中的生理作用。 拟议研究的结果将提供对不寻常的，困难的化学的深入了解，并对C-P天然产物和相关化合物的生物合成产生影响。