CAREER: Combining Chemistry with Bioinformatics to Discover Novel Transformations of Nonproteinogenic Amino Acids

通过这一奖项，化学系的生命过程化学项目资助了北卡罗来纳大学教堂山分校的李波博士，以识别新的、高效的转化，这些转化产生的氨基酸不会被整合到蛋白质中，即所谓的非蛋白生成氨基酸或NAA。NaAs在所有生命形式中都有生产，并在农业中得到了广泛的应用。然而，大多数NAA是如何产生的仍不得而知。快速基因测序为重振对这些从根本上有趣和具有工业重要性的化合物的研究提供了机会。李博士研究了相关的酶，并采用了可能导致发现新的酶催化化学的方法，化学家和合成生物学家可以利用这种化学方法以环境友好的方式构建有用的分子。研究和教育活动吸引研究生和本科生参与科学研究，并在化学和生物的界面上发展跨学科技能。与莫尔黑德天文馆和科学中心合作的推广活动特别关注北卡罗来纳州的农村和服务不足的地区，接触到不同社会经济地位的广泛受众，使儿童和成年人能够展示他们自然的好奇心，并了解化学如何影响他们周围的世界。这项研究项目描述了NAA生物合成中的新的化学转化，并探索这些转化作为工具来构建设计的天然产品。李博士的目标是将NAA生物合成中新化学的发现与使用生物化学、生物信息学和微生物遗传学工具的下一代科学家的培训相结合。作为迈向这一目标的第一步，本研究描述了鉴定和表征氧乙烯基甘氨酸生物合成中新的酶转化的目标，氧乙烯基甘氨酸是一类结构独特的NaA。表征了氧乙烯甘氨酸途径中涉及的新的酶功能，重点是涉及产生烯烃和杂原子-杂原子键的不寻常的氧化化学。基因组挖掘方法被用来恢复独特的、被忽视的NAA的生物合成，这些NAA是更大的自然产品的一部分。这些研究的结果将为NAA是如何构建的提供洞察力，并使NAA生物合成酶在生物催化中的使用成为可能。李教授的教育目标是发展细菌新陈代谢，作为本科教育和外展的平台。与莫尔黑德天文馆和科学中心合作，李博士和她的研究生开发了一个旅行箱，其中包含关于细菌着色的互动活动，作为一种工具，向北卡罗来纳州的儿童和成年人介绍细菌化学研究的价值和兴奋。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Bo Li from the University of North Carolina at Chapel Hill to identify novel, efficient transformations that create amino acids that do not become incorporated into proteins, the so called nonproteinogenic amino acids or NAAs. NAAs are produced across all life forms and have found broad applications in agriculture. How most NAAs are made, however, remains unknown. Rapid genetic sequencing has provided opportunities to reinvigorate investigations of these fundamentally interesting and industrially important compounds. Dr. Li studies the enzymes involved and employs may lead to the discovery of novel enzyme-catalyzed chemistry that can be used by chemists and synthetic biologists to construct useful molecules in an environmentally friendly way. The research and educational activities engage graduate and undergraduate students in scientific research, and develop interdisciplinary skills at the interface of chemistry and biology. Outreach activities in partnership with the Morehead Planetarium and Science Center with special focus on rural and underserved areas of North Carolina reach a wide spectrum of audiences of different socioeconomic status, enabling children and adults to demonstrate their natural curiosity and understand how chemistry impacts the world around them.This research project characterizes the novel chemical transformations in NAA biosynthesis and explores these transformations as tools to construct designer natural products. Dr. Li's goal is to integrate the discovery of novel chemistries in NAA biosynthesis with the training of next-generation scientists using the tools of biochemistry, bioinformatics and microbial genetics. As a first step toward this goal, this research describes objectives to identify and characterize novel enzyme transformations in the biosynthesis of oxyvinylglycines, a class of structurally unique NAAs. Novel enzyme functions involved in oxyvinlyglycine pathways are characterized, with a focus on unusual oxidation chemistries involved in generating alkenes and heteroatom-heteroatom bonds. A genome-mining approach is used to resurrect the biosynthesis of unique, neglected NAAs that are part of larger natural products. Results from these studies will provide insights into how NAAs are constructed and enable the use of NAA biosynthetic enzymes in biocatalysis. Professor Li's educational objective is to develop bacterial metabolism as a platform for undergraduate education and outreach. In collaboration with the Morehead Planetarium and Science Center, Dr. Li and her graduate students develop a traveling suitcase containing interactive activities on bacteria pigmentation, which is used as a tool to introduce the value and excitement of research on bacterial chemistry to children and adults across North Carolina.