Engineering Multifunctional Enzymes And Investigating Versatility Of Enzymatic Halogenation For Nonribosomal Peptide Synthesis
Invited Lecture (IL)
Biosynthesis and Molecular Biology of Natural Products
Date and time:
17:00 to 17:35 on 11/09/2021
Nonribosomal peptides are natural products biosynthesized by multi-modular enzymatic assembly-lines comprised of domains performing varied activities. Adenylating enzymes play a key role in dictating the identity of building blocks to be incorporated in growing peptides during nonribosomal peptide biosynthesis. To increase the structural diversity of the products it generates, Nature has evolved unique interrupted adenylating enzymes capable of performing both adenylation and methylation reactions. We will present our biochemical and structural work towards understanding the mechanism by which these unique enzymes function and our efforts towards engineering novel interrupted enzymes with adenylating and methylating activities. Additionally, we will discuss halogenation, an important biotransformation and a highly promising transformation in medicinal chemistry, which could lead to improvement in pharmacological and pharmaceutical properties of compounds or enabling further modifications by using the halogen as a reactive handle. In the last decade, halogenases have emerged as highly promising tools that may serve as an alternative or the only route to halogenating some molecules, especially natural products. Our biochemical and structural study of two halogenases will be presented.
University of Kentucky
Sylvie Garneau-Tsodikova obtained her Ph.D. in Chemistry in 2003 from the University of Alberta (Prof. John C. Vederas). She then pursued her postdoctoral studies with Prof. Christopher T. Walsh at Harvard Medical School. In 2006, Sylvie joined the University of Michigan as the John G. Searle Assistant Professor of Medicinal Chemistry at the College of Pharmacy and the Life Sciences Institute. In 2013, she relocated to the University of Kentucky as an Associate Professor of Pharmaceutical Sciences with tenure at the College of Pharmacy, where she is now the Patrick P. DeLuca Pharmaceutical Technology Professor and Assistant Vice President for Research. Her work focuses on understanding and combating bacterial and fungal resistance. Her expertise is in medicinal chemistry and her group also works at the interface of biochemistry and microcrobiology. She is on the International Advisory Board of ChemMedChem, an Associate Editor for RSC Medicinal Chemistry, and a member of the editorial board of Journal of Biological Chemistry and ACS Infectious Diseases. She has published >150 manuscripts. She is the recipient of numerous awards including the Vahlteich Research Award and NSF CAREER Award. She has given >100 invited talks and plenary lectures on her work worldwide (e.g., Brazil, Canada, China, England, Israel, Egypt, India, Jamaica, Mexico, Scotland, South Africa, and USA). As a result of her passion/work for outreach, she is an AAAS Leshner Fellow for public engagement as well as an AAAS/Lyda Hill IF/THEN ambassador. She is striving and working hard for equality and inclusivity in science.
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