Professor Yang Yang (UC Santa Barbara)

Title: Complexity-Generating Biocatalysis Through Enzyme Design and Evolution

Atstract: The past decade has witnessed breathtaking progress in the development of University of California Santa Barbara biocatalytic reactions with reactivities not previously known in native enzymology. Despite these advances, developing efficient, stereoselective, and complexity-generating biocatalytic processes that remain beyond the reach of synthetic organic and organometallic chemistry continues to be a major challenge. In this seminar, I will present our latest efforts using enzyme repurposing and de novo enzyme design to address these limitations. 

Building on pyridoxal radical biocatalysis developed in our laboratory, we have established stereoselective, protecting-group-free access to useful chiral amino acids and amines, including molecules bearing stereochemical triads and contiguous tetrasubstituted stereocenters that remain difficult to prepare by existing chemical or biological methods. The ability to perform complexity-generating biocatalytic synthesis in a combinatorial fashion represents a synthetically valuable advance and opens new opportunities for the broader adoption of biocatalysis in medicinal chemistry. We further demonstrate that accelerated exploitation of biocatalyst–photocatalyst synergy provides a powerful strategy for discovering unexpected catalytic reactivity and reaction outcomes.

Finally, I will describe our recent efforts to integrate chemical and biochemical insights with generative de novo protein design to create metalloprotein catalysts from first principles. These designed catalysts enable synthetically useful cross-coupling reactions to proceed with enzymatic stereocontrol, illustrating the potential of de novo enzyme design to expand biocatalysis beyond the reaction space accessible to natural enzymes.

Biography: Dr. Yang received his Ph.D. degree in Organic Chemistry in 2016 under the guidance of Prof. Steve Buchwald at MIT. As an NIH Postdoctoral Fellow working with Prof. Frances Arnold at Caltech, Dr. Yang studied biocatalysis and protein engineering. Dr. Yang started his independent career in 2020 in the Department of Chemistry and Biochemistry at the University of California Santa Barbara, where he was promoted to Associated Professor in the Departments of Chemistry and Biochemistry and Bioengineering in 2025. Using an interdisciplinary approach combining synthetic chemistry, synthetic biology, computational chemistry and computational biology, the Yang lab reprograms nature’s biosynthetic machineries and designs de novo protein catalysts to access reaction space well beyond the native biochemical landscape. The Yang lab coined metalloredox radical biocatalysis (2021) and pyridoxal radical biocatalysis (2023) as general strategies to advance novel enzyme functions not previously known in nature, including those which are unknown in both chemistry and biology. Dr. Yang is a recipient of the Regent’s Junior Faculty Fellowship Award (2021), Faculty Career Development Award (2022), National Science Foundation (NSF) CAREER Award (2022), National Institutes of Health (NIH) Maximizing Investigators' Research Award (2022), Thieme Chemistry Journals Award (2023), Army Research Office (ARO) Young Investigator Award (2023), Packard Fellowship (2023), Sloan Research Fellowship (2024), Department of Energy (DOE) Early Career Award (2024), Amgen Young Investigator Award (2024), Novartis Early Career Award (2025), Camille Dreyfus Teacher-Scholar Award (2025), Mitsui Chemicals Catalysis Science Award for Creative Work (2026), an NAS Frontiers of Science Fellow (2026) and Cope Scholar Award (2027). Dr. Yang has been an Associate Editor of Organic Letters and a Howard Hughes Medical Institute (HHMI) Freeman Hrabowski Scholar since 2025.