A newly discovered enzyme is helping scientists perform a rare chemical reaction once considered out of reach, potentially paving the way for a new generation of antibiotics, cancer therapies, and sustainable materials.
The enzyme, known as Abx(−)F, was identified by researchers at the School of Life Sciences in Shanghai for its ability to perform a hetero-Diels–Alder (HDA) reaction - a powerful tool in synthetic chemistry that allows scientists to ‘snap’ smaller molecules together to form complex ring structures.
These rings are the building blocks behind advanced medicines and smart materials, from targeted cancer drugs to flexible electronics and responsive gels.
To reveal exactly how the enzyme pulls off this intricate transformation, researchers at The University of Queensland used advanced measurement of atomic positions, including nuclear magnetic resonance and X-ray diffraction, to capture atomic-level 3D structures of the reaction in action.
AIBN structural biologist Professor Mehdi Mobli said Abx(−)F’s ability to perform this reaction will unlock a whole new area of molecular design and discovery.
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“In traditional chemistry labs, analogous structures often require 10 to 20 separate synthetic steps, often involving toxic solvents and complex experiments, ultimately with low success rates.
“By mapping the reaction mechanism and capturing it in 3D models, we’ve shown that Abx(−)F can perform the same transformation in one clean, selective step.”
The team’s findings could reshape synthetic biology by allowing scientists to design biological systems that produce high-value compounds more efficiently and sustainably.
“Now we have access to a complex and synthetically challenging molecular structure via a new enzymatic route,” Professor Mobli said.
“This unlocks opportunities to discover powerful natural products that were previously out of reach using conventional methods – potentially new generations of antimicrobials.”
The international partnership that led to the breakthrough was sparked by AIBN alum Dr Xinying “Sid” Jia, who had previously worked with the Shanghai team during his PhD and later recognised the opportunity to bring UQ’s structural biology expertise into the project.
“From the beginning, I knew this was something special, but we needed deep structural biology to really understand it,” Dr Jia said.
He said the project was a powerful example of what becomes possible through international scientific collaboration.
“Discoveries like this don’t happen in isolation. This was only possible because people in different parts of the world brought their strengths to the table and trusted each other to do what they do best.”
With the enzyme’s structure and function now understood, researchers are already thinking about how it could be adapted and applied.
“Now that we understand how this enzyme works, we can explore how to evolve it or design related enzymes that can access even more of that untapped chemical space.”
The discovery could also reshape biomanufacturing, where enzymes are engineered to replace traditional chemical processes that are costly, energy-intensive, and harmful to the environment.
“It’s a platform for innovation,” Professor Mobli said.
“The tools we’ve developed here could be used to design a whole new generation of enzymes that help us build molecules in smarter, greener ways.”
The research offers new momentum for synthetic biology and green chemistry, as scientists look for cleaner, faster, and more sustainable ways to build the molecular building blocks of future medicines and materials.
This research was published in Nature Chemistry on 22 April 2025 and co-authored by Xiaoli Yan, Xinying Jia, Zhenyao Luo, Shunjia Ji, Meng-Jie Zhang, Hui Zhang, Mingjia Yu, Juli_
