Mechanism and Role of Enzymatic P-Methyl Transfer

通过这一奖项，化学学部的生命过程化学项目资助了华盛顿州立大学的Susan Wang博士，以描述两种磷酸化磷原子的酶所使用的不寻常的化学反应：“p -甲基转移酶”，PhpK和SD 1168。含有碳磷键的化合物（C-P）在农业、工业和医学中起着重要作用。C-P键不易被水破坏，这使得含有这种稳定结构特征的化合物具有商业用途。此外，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。该项目将研究形成碳-磷-碳（C-P-C）键的唯一已知酶的生理作用，即“p -甲基转移酶”。本科生和研究生将在化学和生物学方面接受广泛的多学科培训。这些受训者还将参加一个外联方案，向农村和/或低收入学龄前儿童介绍生命科学，作为一种潜在的职业道路。这里的重点是两种p -甲基转移酶，PhpK和SD 1168，它们将磷原子甲基化。酶都能产生重要的自然产品phosphinothricin前兆,广谱除草剂和抗生素的属性。PhpK和SD 1168都被认为是利用维生素B12和自由基化学组合形成C-P-C键序列。来自海洋反硝化希瓦氏菌的SD 1168比PhpK表现出更广泛的底物特异性。虽然其真正的生物学功能尚不清楚，但SD 1168是未来工程努力生产新的C-P-C化合物的潜在候选者。结合光谱、合成、分子生物学、微生物学和晶体学技术的多方面合作方法将用于确定p甲基化的酶促机制，并查明SD 1168在其宿主生物中的生理作用。拟议的研究结果将为不寻常的、困难的化学提供见解，并对C-P天然产物和相关化合物的生物合成产生影响。

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.