December 16-21, 2021 – Honolulu, HI. The application of physical organic chemistry and mechanistic thinking to the investigation of biological systems provides a strong intellectual framework for understanding the molecular logic of the chemical transformations that occur in living organisms. In turn, these ideas have driven methodological advances in protein engineering, drug discovery, in the evolution of enzymes capable of catalyzing novel reactions, and in the creation of organisms with use in a wide variety of industrial applications. Furthermore, the principles of reactivity have formed the basis for the design and application of new chemical tools to probe biological function in both health and disease. This symposium will bring to light timely and significant results from studies focused on the use of small molecules in studying and manipulating biological systems, and the creation of microorganisms with novel chemical capabilities (e.g., enzyme mechanisms and inhibitor design principles, activity profiling in proteomes, alteration of biosynthetic pathways for creating new chemical entities, and the design and implementation of expanded genetic alphabets within microorganisms). We will identify and showcase young researchers alongside more established names in this field, and the program will include a dedicated session to highlight to work of younger investigators, including post-doctoral researchers.