Engineering Photoenzymes for New-to-Nature Asymmetric Radical Processes

PHOTO-BIO-ENG aims to develop entirely new strategies for the stereoselective synthesis of complex chiral molecules. We will achieve this by combining biocatalysis and photocatalysis to generate photoenzymes for visible-light-driven radical processes. Utilizing directed evolution and high-throughput experimentation, we will create highly efficient and stereoselective photoenzymes capable of catalyzing transformations that are currently inaccessible to small-molecule catalysts and unachievable via ground-state thermal pathways. Our approach will use enzymes as green catalysts and visible light as a renewable energy source, with environmentally benign reaction conditions (ambient temperatures, aqueous solvents). By merging photochemical methodology with enzyme catalysis, we aim to demonstrate novel chemical transformations that produce chiral products with multiple stereocenters and excellent stereocontrol. This project will establish a highly effective and sustainable synthetic methodology, contributing to the advancement of green chemistry practices.Collaboration with Johnson & Johnson will facilitate the development of photoenzymatic processes to yield chiral molecules with biologically relevant scaffolds. PHOTO-BIO-ENG combines the fellow’s experience in enzymatic catalysis and directed evolution with the host’s expertise in photo-triggered asymmetric radical processes. The interdisciplinary nature of the project will significantly enhance the fellow's expertise, providing comprehensive training and positioning them strongly for future career advancements.