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

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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.