Chemical Biology Seminar: Dr. Grace Kenney, Harvard University
Host: Steven Banik
"Identifying new metalloenzyme families involved in natural product biosynthesis"
About the Seminar:
Microbially produced natural products have been a major source of and inspiration for pharmaceutical agents over the last century. The enzymes that make these complex compounds often employ unusual biochemical strategies, and the origins of many natural products remain entirely unknown. The characterization of new biosynthetic enzymes broadens our understanding of the basic chemistry microbes perform and gives us vital information needed to identify pathways that produce novel bioactive compounds.
My research has combined bioinformatics, bioinorganic chemistry, and bacteriology to explore metalloenzymes from unstudied protein families that carry out unusual redox reactions. In this seminar, I will discuss how I have applied this interdisciplinary approach beginning in my graduate career when I elucidated the biosynthesis, regulation, and transport of the copper-binding peptidic natural product methanobactin. En route, I characterized the first member of a large and diverse family of iron enzymes responsible for unusual oxidative post-translational cysteine modifications. More recently, as a postdoctoral researcher, I have identified and characterized a new heme enzyme family that forms nitrogen-nitrogen bonds in the otherwise structurally unrelated natural products fosfazinomycin and lomaiviticin. As part of this work, I have additionally identified the biosynthetic pathway for the broad-spectrum antibiotic negamycin. These projects provide a paradigm for accelerating the discovery of the products, roles and reaction mechanisms of new types of microbial enzymes.\
About the Speaker:
Dr. Grace Kenney is currently a postdoctoral researcher and a Merck Fellow of the Damon Runyon Cancer Research Foundation, working in the laboratory of Prof. Emily Balskus at Harvard University. Dr. Kenney earned an S.B. in Chemistry from the Massachusetts Institute of Technology, after studying the chemotherapeutic natural product bleomycin in the laboratory of Prof. JoAnne Stubbe. As a graduate student, Dr. Kenney joined the laboratory of Prof. Amy Rosenzweig at Northwestern University, investigating the production and biological roles of copper-binding natural products, ultimately receiving a Ph.D. in Biological Sciences. Support for this research came from several sources, including an American Heart Association Predoctoral Fellowship and a Northwestern University Presidential Fellowship. Dr. Kenney’s postdoctoral work in the Balskus group has focused on new enzyme families that form nitrogen-nitrogen bonds in diverse natural products.