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

通过这一奖项，化学学部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，以确定新的、有效的转化，这种转化产生的氨基酸不会被合并到蛋白质中，即所谓的非蛋白质氨基酸或NAAs。NAAs可以在所有生命形式中产生，并在农业中得到广泛应用。然而，大多数NAAs是如何产生的仍不得而知。快速基因测序为这些从根本上有趣且具有重要工业意义的化合物的研究提供了机会。李博士研究所涉及的酶和使用可能导致新的酶催化化学的发现，化学家和合成生物学家可以用一种环保的方式来构建有用的分子。研究和教育活动使研究生和本科生参与科学研究，并在化学和生物学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开展的外展活动特别关注北卡罗莱纳州的农村和服务不足地区，吸引了不同社会经济地位的广泛受众，使儿童和成人能够展示他们天生的好奇心，并了解化学如何影响他们周围的世界。本研究项目描述了NAA生物合成中的新化学转化，并探索了这些转化作为构建设计天然产物的工具。李博士的目标是利用生物化学、生物信息学和微生物遗传学的工具，将NAA生物合成中新化学物质的发现与下一代科学家的培训结合起来。作为实现这一目标的第一步，本研究描述了识别和表征氧乙烯基甘氨酸（一类结构独特的NAAs）生物合成中的新型酶转化的目标。新的酶功能涉及到氧乙烯基甘氨酸途径的特征，重点是不寻常的氧化化学参与生成烯烃和杂原子-杂原子键。基因组挖掘方法被用来复活独特的生物合成，被忽视的NAAs是更大的天然产物的一部分。这些研究的结果将为NAA如何构建以及NAA生物合成酶在生物催化中的应用提供见解。李教授的教育目标是发展细菌代谢作为本科教育和推广的平台。在与莫尔黑德天文馆和科学中心的合作中，李博士和她的研究生开发了一个包含细菌色素沉着互动活动的旅行箱，作为向北卡罗莱纳的儿童和成人介绍细菌化学研究的价值和兴奋的工具。

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.