A pioneering research lab at the University of Illinois Urbana-Champaign has achieved another milestone using light-driven enzymatic reactions to convert simple biological building blocks into valuable chemicals.
The researchers, part of the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), developed a clean, efficient way to make complex chemicals called chiral ketones through photocatalysis — combining bioengineered enzymes with light to create novel reactions.
"Enzymes are powerful catalysts, but they are limited by the narrow scope of their reactivity for industrial applications. In this work, we have successfully demonstrated that enzymes with new-to-nature reactivity can be created by light," said CABBI Conversion Theme Leader Huimin Zhao, corresponding author for the study. Zhao, whose lab has used that approach to produce other valuable chemical reactions, is Professor of Chemical and Biomolecular Engineering (ChBE), Biosystems Design Theme Leader at the Carl R. Woese Institute for Genomic Biology (IGB), and Director of the NSF Molecule Maker Lab Institute, NSF iBioFoundry, and NSF Global Center for Biofoundry Applications at Illinois.
The new study, published in Nature Catalysis, was led by first authors Zhengyi Zhang and Maolin Li, Postdoctoral Research Associates with CABBI, ChBE, and IGB. CABBI is a Bioenergy Research Center funded by the Department of Energy (DOE).
Many useful chemicals — especially in agrochemicals and medicines — exist in two mirror-image forms, like left and right hands. These are called chiral molecules, and often only one "hand" is effective or safe. While chemists can build chiral molecules from scratch using a strategy called asymmetric catalysis, this process can be complex and costly.
In contrast, making a racemic mixture — a 50:50 blend of both mirror-image forms — is often easier and cheaper. That's why another approach, called enantioconvergent catalysis, is so valuable: It allows both versions in a racemic mixture to be converted into the product of one chirality. However, most current methods can only do this when the stereocenter is near the reactive site of the molecule. Reaching remote stereocenters — parts that are farther away and harder to access — is still a major challenge.
In this study, scientists solved the problem by using a photoenzymatic reaction. When exposed to light, the enzyme generates a nitrogen-centered radical — a very reactive intermediate that can break the remote chiral carbon-hydrogen bond through a process called 1,5-hydrogen atom transfer.
The enzyme then carefully rebuilds this bond of the molecule by hydrogen atom transfer, choosing one preferred "handedness." This method allows both forms of the starting material to be funneled into the same chiral product, even when the original chiral center is far from the reaction center – offering a precise and eco-friendly way to make chiral molecules with complicated structures.
"Everyone was puzzled at first — we were studying a different reaction involving nitrogen-centered radicals when this unexpected result appeared," Zhang said. "I'm glad we didn't miss this interesting discovery."
Importantly, the ketones used in this research can be readily derived from C6 and C12 fatty acids found in plant biomass. This creates a new opportunity to transform renewable carbon sources like bioenergy crops into high-value molecules, supporting CABBI's mission to build sustainable biomanufacturing platforms based on plant-derived feedstocks.
This approach aligns with the DOE's broader goals of developing innovative technologies for a sustainable bioeconomy. It offers a cleaner, more efficient way to make the specific "handed" forms of molecules needed for medicines, agrochemicals, and other everyday products. By using light and enzymes to convert cheap, easy-to-make mixtures into high-value compounds, the method can reduce costs and chemical waste — making it both practical and environmentally friendly.
Co-authors on the study included CABBI's Wesley Harrison, Jingxia Lu, and Yujie Yuan, all of ChBE and IGB; and Zhenxiang Zhao of the Department of Chemistry at Illinois.
