AI and Robotics Revolutionize Enzyme Improvement at Illinois Lab

CHAMPAIGN, Ill. — Researchers at the University of Illinois Urbana-Champaign have embarked on a groundbreaking approach to enzyme improvement by integrating artificial intelligence (AI) with automated robotics and synthetic biology. This innovative methodology aims to enhance the performance of industrial enzymes, which are crucial in various sectors including energy production, therapeutics, and consumer products. The team, led by Professor Huimin Zhao of the Department of Chemical and Biomolecular Engineering, reported their findings in a recent issue of *Nature Communications* on July 2, 2025.

Enzymes are proteins that facilitate numerous biochemical processes. However, their application has been limited by challenges related to efficiency and specificity. "Enzymes have been increasingly used in energy production, therapeutics, and even in consumer products like laundry detergent, but significant limitations remain. Our technology addresses these limitations efficiently," stated Zhao, who is also affiliated with the Carl R. Woese Institute for Genomic Biology.

The research team has developed a model that predicts modifications needed to enhance enzyme function. "Improving protein function, particularly enzyme functionality, is complex because it often involves multiple synergistic mutations," Zhao explained. This integrated approach leverages AI to create a smaller library of potential enzyme variants, thus eliminating the need for random searches across vast protein sequences.

According to Nilmani Singh, co-first author of the study, "In a typically sized enzyme, the possible number of variations is larger than the number of atoms in the universe. By employing AI, we can streamline the identification of potentially useful mutations."

To facilitate this process, the researchers utilized the iBioFoundry, a facility at the University of Illinois dedicated to the rapid engineering and testing of biological systems. Zhao directs this center, which is supported by the National Science Foundation (NSF). The process begins with the AI tool generating suggestions for enzyme modifications based on existing structural datasets. These suggestions are then implemented using automated protein synthesis machines at the iBioFoundry, followed by rapid functional testing of the variants.

Stephan Lane, manager of the iBioFoundry and co-first author, emphasized the lab's goal of achieving a self-driving lab environment. "This setup allows the lab to design, make, and test proteins autonomously, with AI algorithms guiding the design and robotics handling the construction and testing phases."

The researchers successfully enhanced two industrial enzymes using this method. One enzyme, designed to improve the nutritional content of animal feed, exhibited a 26-fold increase in activity, while another catalyst used in industrial chemical synthesis achieved a 16-fold increase in activity and a 90-fold improvement in substrate preference.

"Our approach is not limited to just these two enzymes; it can be generalized to a wide range of proteins. We only need the protein sequence and an assay to begin the process," Zhao noted.

Future plans for the research team include refining their AI models and upgrading the iBioFoundry's equipment to accelerate the synthesis and testing processes. A user-friendly interface has also been developed to allow researchers from diverse backgrounds to utilize the system without needing programming expertise; they can simply describe their needs in English. Graduate student Tianhao Yu, a co-author, remarked, "The motivation behind the user interface is to democratize access to this technology for researchers who may not have technical training."

This research received support from the National Science Foundation and the U.S. Department of Energy, underscoring the potential of AI and automation in advancing enzymatic applications across various industries. As the team continues to innovate, the implications of their findings could significantly impact drug development, energy innovation, and sustainability efforts worldwide.