Rudi Fasan was recently recruited to Texas as a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research and the Robert A. Welch Distinguished Chair in Chemistry at the University of Texas at Dallas. He focuses on developing more efficient, sustainable and innovative enzyme-based approaches for chemical synthesis. His research explores the use of biocatalysis to generate complex, biologically active molecules with pharmaceutical applications, such as the synthesis of compounds for cancer and malaria treatments.
A key focus of Dr. Fasan’s research is the development of biocatalytic methods for synthesizing chiral molecules—critical building blocks in high demand for the discovery, manufacture and synthesis of new drugs by the pharmaceutical industry. Traditionally, organic chemists have relied on chemical catalysis using rare and sometimes toxic metals. Dr. Fasan’s research has pioneered the use of enzymes to achieve these transformations in a more sustainable and selective manner.
About a decade ago, his team began exploring “new to nature” chemistry, a concept at the forefront of the biocatalysis field that repurposes natural enzymes—or even non-enzymatic metalloproteins—to carry out chemical transformations that do not occur naturally in biological systems. This approach has significant advantages, including environmental sustainability (especially when replacing rare or toxic metals in reactions) and enhanced selectivity in molecular synthesis. For example, his work on enzymatic “new to nature” chemistry has led to more efficient methods for producing complex chiral molecules with high stereoselectivity.
With Welch support, Dr. Fasan’s group is expanding these approaches to new classes of enzymes, aiming to unlock new synthetic capabilities that were previously thought impossible. His work has already demonstrated that enzymatic systems can rival, and in some cases surpass, traditional synthetic methods.
A central theme in modern organic chemistry is the selective functionalization of carbon–hydrogen (C–H) bonds to develop high-value compounds in a more efficient, less wasteful reaction. Dr. Fasan has engineered enzymes that catalyzed challenging C−H functionalization reactions for bioactive molecules with record-high efficiency.
While catalysis with engineered enzymes provides more efficient routes for the production of active pharmaceutical agents, the potential of biocatalysis to assist in early-stage drug discovery campaigns remains largely untapped.
“It’s uncharted territory. There are many opportunities where, by using chemical intuition, we can utilize enzymes for functions they did not evolve for. We find that incredibly exciting because it’s really open to the creativity of organic chemists,” said Dr. Fasan. “There’s so much to discover—we’ve just scratched the surface of what’s possible. One of the key benefits granted by the Welch Chair is the opportunity to explore.”
Recent advances in Dr. Fasan’s lab have led to the discovery of novel bioactive molecules with promising anticancer properties. Moving forward, his team aims to elucidate the molecular mechanisms underlying their selectivity toward specific cancer cell lines, with the ultimate goal of developing more targeted cancer therapies.
“Part of my research is working on the discovery of new bioactive molecules, with a specific focus on anti-cancer and antiviral compounds, in addition to chemical synthesis and for asymmetric synthesis. And with one of the best medical schools nearby, there are many opportunities for synergy.”
Dr. Fasan is passionate about fostering interdisciplinary collaborations. At UT Dallas, he has played a key role in establishing the Center for High-Throughput Reaction Discovery and Synthesis (HT-RDS), an initiative designed to accelerate the discovery of new methods and catalysts by screening many reactions simultaneously and experimenting with machine learning.
“It has been amazing to connect with this vibrant community of chemists across Texas and through The Welch Foundation. That was one of the key factors that attracted me to Texas.”