Edwin Alfonzo Uses Biology to Tackle Chemistry’s Hard Problems

Edwin Alfonzo, assistant professor of Chemistry, really wanted to make molecules. 

He discovered this passion in an organic chemistry class at the University of Massachusetts-Lowell. “I was a sophomore, and I remember sitting in that classroom, putting together chemical routes to target the molecules the professor assigned to us, and thinking with amazement, ‘Wow, we humans really have an incredible level of control.’” 

Deeply moved by the realization that chemistry allows us to control matter to such a high level of precision, Alfonzo pursued a Ph.D. at Boston University researching how to make lignans — small molecules found in seeds, fruits and vegetables. These molecules are bioactive, opening the door to their potential therapeutic use. The best-known molecule Alfonzo worked on during his Ph.D. is the FDA-approved anti-cancer agent podophyllotoxin. 

While studying lignans, Alfonzo realized that enzymes are much better organic chemists than humans. He became fascinated by biocatalysis, using enzymes from living systems to make chemical reactions cleaner, more efficient and more precise. 

After graduation, Alfonzo worked as a postdoc with Frances Arnold, who in 2018 became the first American woman to win the Nobel Prize in Chemistry for pioneering a method called “directed evolution.” 

“Directed evolution allows us to take enzymes from organisms that live in any ecosystem in the world — from under our feet, from volcanoes, from deep in the ocean — and bring them into the lab and improve them to carry out specific tasks,” Alfonzo said. “I wanted to learn that process so I could use enzymes to make molecules.” 

This is what Alfonzo hopes to do at Duke: Bring his unique expertise, both in organic chemistry and in biocatalysis, to solve problems in the production of chemicals by using enzymes improved through directed evolution. 

“I'm a very target-oriented chemist,” he said. “I choose to work with molecules that I believe will lead to some tangible application. I'm not just limited to molecules in the pharmaceutical world. For example, directed evolution could be used in the production of agrochemicals to make plants grow better, or to create or break down polymers. You can use biocatalysts in many contexts.” 

Alfonzo is passionate about teaching, both in the classroom and in his lab. “I want students to understand that enzymes are very powerful catalysts that can be used to address important problems. When I was a student, I rarely learned about the use of enzymes in real-world applications, focusing mostly on chemical approaches to solving problems. I want to show students that now there are also many biological solutions to consider.” 

This year Alfonzo will be setting up his research group, and he’s looking forward to collaborating with colleagues in Biology and Biomedical Engineering. “I can hit the ground running, because the tools and ideas that I use are already established at Duke,” he said. 

In addition to Alfonzo, the department of Chemistry is also welcoming Assistant Professor Evert Njomen to the faculty this year. 

"The addition of Professors Edwin Alfonzo and Evert Njomen increases our department's footprint in chemical biology and organic synthesis,” said Michael Fitzgerald, chair of the department. “Edwin brings a new perspective to chemical synthesis. His work at the forefront of biocatalysis will identify new enzyme catalysts to perform high-value organic transformations that are new-to-nature. I can’t wait to see all the exciting new research that comes out of these new labs."