Enzymes are increasingly being used in environmentally friendly and sustainable processes to produce key chemical building blocks for a variety of industries, including pharmaceuticals, chemicals, and biofuels. These enzymes have several advantages over traditional chemical methods, such as milder reaction conditions, higher selectivity, and lower environmental impact.
Using light energy to activate natural enzymes can assist scientists in developing novel enzymatic reactions that support environmentally friendly biomanufacturing – the production of fuels, plastics, and valuable chemicals from plants or other biological systems.
Using this photoenzymatic approach, researchers created a clean, efficient method for synthesizing critical chemical building blocks known as chiral amines, resolving a long-standing challenge in synthetic chemistry.
Researchers from the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), a U.S. Department of Energy-funded Bioenergy Research Center; the Department of Chemical and Biomolecular Engineering (ChBE) at the University of Illinois Urbana-Champaign; and Xiamen University in China collaborated on the study, which was published in Nature Catalysis.
It was led by CABBI’s Zhengyi Zhang, Postdoctoral Research Associate with ChBE Professor Huimin Zhao, CABBI’s Conversion Theme Leader and an affiliate of the Carl R. Woese Institute for Genomic Biology (IGB); and Jianqiang Feng and Binju Wang of the College of Chemistry and Chemical Engineering, Xiamen University.
It’s a new reaction that is extremely difficult to achieve with a chemical catalyst because we are producing chiral compounds, and there are no natural enzymes that can catalyze that reaction. In this work, we created an artificial enzyme that can achieve that unique reaction.
Huimin Zhao
Their research centered on hydroamination, a complex chemical reaction that can be used to generate chiral amines, which have numerous applications in the synthesis of agrochemicals and other products. The researchers created a photoenzymatic system capable of controlling unstable nitrogen-centered radicals in a reaction known as enantioselective intermolecular radical hydroamination, which had previously been considered a major challenge in chemistry. Because electrons prefer to be in pairs, radicals are atoms or molecules with at least one unpaired electron, making them highly chemically reactive.
The process of adding an amino group (a nitrogen atom bonded to one or two hydrogen atoms) to an unsaturated organic compound is known as hydroamination. Hydroamination reactions can currently be carried out using metal- or photo-catalysts, which are substances used to accelerate chemical reactions. While photocatalysis has advantages over other methods in that it uses light as the energy source and eliminates the need for expensive and toxic metals, it has not previously been used in intermolecular hydroamination reactions for chiral amines due to the difficulty in controlling the nitrogen-centered radicals – key intermediates in the catalytic process.
To address this issue, the researchers turned to natural enzymes, which are proteins found in living organisms that catalyze reactions through a process known as biocatalysis. Natural enzymes can produce and control free radicals in a variety of biological processes. Furthermore, due to the high selectivity of biocatalysis, researchers can use enzymes to act on specific substrates and generate valuable target products. Zhao’s lab has had success using photocatalysis to steer that process and generate new enzyme reactivity.
The CABBI researchers chose the ene-reductase enzyme, which they had previously used with other substrates to achieve different reactions, for this study. They successfully used natural light to repurpose an ene-reductase to achieve intermolecular radical hydroamination with high enantioselectivity (the ability to target a mirror-image molecule known as an enantiomer).
“It’s a new reaction that is extremely difficult to achieve with a chemical catalyst because we are producing chiral compounds, and there are no natural enzymes that can catalyze that reaction,” Zhao explained. “In this work, we created an artificial enzyme that can achieve that unique reaction.”
Most biological compounds are “chiral,” which means that a flipped or mirrored copy cannot be completely superimposed on top of the original molecule (like a left and right hand). Many agrochemical products rely on chirality; for example, in some herbicides, one enantiomer may have greater herbicidal activity and selectivity than the other. As a result, it is critical to develop efficient methods for producing chiral molecules.
The findings have practical applications for CABBI’s research to develop efficient methods for transforming leaves and stems from bioenergy grasses into high-value manufacturing products. Fatty acids that CABBI researchers derive from plant biomass can be readily converted into the unsaturated compounds used in this study, and therefore could potentially be upgraded into chiral amines.
More broadly, the discovery of this new photoenzymatic system shows that chiral amines – precursors for other valuable molecules – can be produced in the lab from fatty acid-derived material, providing a promising platform for biomanufacturing. It will allow for more research into converting fatty acids into chiral amino acids, which can be used to make agrochemicals and other molecules and materials.
The CABBI team has taken a giant step toward understanding the fundamentals of this system by collaborating with researchers all over the world, according to Zhang. “I am very excited to be working with the team to study this reaction, which we believe will lead to new discoveries involving nitrogen-centered radicals.”
