In the quiet hum of a laboratory, a team of researchers saw an opportunity where others had only seen a dead-end. Their quest? To harness the raw power of sunlight and use it to spark life into nature's own micro-machines: enzymes. Their ground-breaking method, born from a blend of creativity and innovation, promises to light up the field of eco-friendly biomanufacturing, potentially revolutionizing the way we produce everything from fuels to plastics and valuable chemicals, all from the unassuming beginnings of plants and other biological systems. Their groundbreaking journey began with the seemingly impossible task of synthesizing crucial chemical building blocks known as chiral amines, but it ended in a landmark discovery that has broken down longstanding barriers in synthetic chemistry.

The breakthrough research, published in Nature Catalysis, involved a collaborative effort by researchers from the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), the Department of Chemical and Biomolecular Engineering at the University of Illinois Urbana-Champaign, and Xiamen University in China.

The team concentrated their efforts on hydroamination, a complex chemical reaction employed in the production of chiral amines vital in the synthesis of agrochemicals and a host of other products. The researchers constructed a photoenzymatic system capable of controlling unstable nitrogen-centered radicals, offering a fresh approach to the reaction known as enantioselective intermolecular radical hydroamination.

“Since the discovery of the Hofmann–Löffler–Freytag reaction more than 130 years ago, both the structure and reactivity of nitrogen-centered radicals have been widely studied, the authors wrote. “Nevertheless, catalytic enantioselective intermolecular radical hydroamination remains a challenge due to the existence of side reactions, the short lifetime of nitrogen-centered radicals, and the lack of understanding of the fundamental catalytic steps. In the laboratory, nitrogen-centered radicals are produced with radical initiators, photocatalysts, or electrocatalysts. In contrast, their generation and reaction are unknown in nature.” 

The authors continued, stating in their paper, “Here we report a pure biocatalytic system for the photoenzymatic production of nitrogen-centered radicals and enantioselective intermolecular radical hydroaminations by successfully repurposing an ene-reductase through directed evolution. These reactions progress efficiently at room temperature under visible light without any external photocatalysts and exhibit excellent enantioselectivities”

"Creating an artificial enzyme for this unique reaction is a significant achievement. This was a difficult reaction to perform using a chemical catalyst because we were producing chiral compounds without natural enzymes to catalyze the reaction," stated Huimin Zhao, a leading researcher in the study.

Chiral compounds, such as DNA molecules, amino acids, and many agrochemicals, are of significant importance as mirrored copies (enantiomers) can possess varying degrees of effectiveness, as evidenced in certain herbicides. Consequently, efficient methods to produce chiral molecules are crucial.

In addition to this, the results of this innovative research have broader implications for CABBI's work on developing efficient methods to convert bioenergy grasses into high-value manufacturing products. CABBI researchers are hopeful that fatty acids derived from plant biomass could potentially be upgraded into chiral amines.

More broadly, the discovery of this new photoenzymatic system sets the stage for producing chiral amines from fatty acid-derived material in a lab, representing a promising platform for biomanufacturing. This will expedite further investigation into upgrading fatty acids into chiral amino acids, which is critical for the production of agrochemicals, other molecules, and materials.

As collaborative research efforts with international teams continue, the CABBI team is making strides in understanding this revolutionary system. Zhengyi Zhang, the lead of the project, voiced his excitement to further delve into this reaction, confident it will catalyze more discoveries involving nitrogen-centered radicals.

"We aspire to discover new reactions that enzymes can catalyze, particularly using the biomass produced by CABBI. We hope this novel method we developed will be adopted by companies for product manufacturing," Zhao concluded.