Boronic acid has been a staple in organic chemistry for many years despite not being found in any organism. Gerard Roelfes, a Professor at the University of Groningen, and his team created an enzyme with a boronic acid reactive center using directed evolution to enhance its selectivity and catalytic power. Enzymatic reactions are more sustainable, occurring at lower temperatures and without toxic solvents. This study was published in Nature on May 8th, showcasing the potential of boronic acid in enzymes.
The use of boron in organic chemistry dates back several decades and was recognized with a Nobel Prize in 1979. While interest in boron as a catalyst has increased, its application in the chemical industry remains limited due to slow catalysis and challenges with enantioselective reactions. Chiral molecules, with two mirror image forms like left and right hands, are crucial in drug development, where each version can have different effects. Producing the correct chiral form is essential for pharmaceuticals.
Roelfes and his team sought to introduce boron into enzymes to enable selective catalysis. They utilized an expanded genetic code to incorporate a non-natural amino acid containing a boronic acid group into an enzyme. This approach allowed precise placement of the amino acid in the protein structure. Through directed evolution, the team enhanced the enzyme’s efficiency, resulting in faster catalysis with high enantioselectivity. The study in Nature serves as a proof of principle for utilizing boron’s catalytic potential in enzymes.
The pharmaceutical industry is increasingly turning to biocatalysis for sustainable drug production. Research at the University of Groningen focuses on creating biocatalytic solutions to replace traditional chemical reactions. With various research groups dedicated to this work, efforts are underway to develop boronic acid enzymes and other new-to-nature enzymes. Roelfes and his team will continue their work to advance biocatalysis and support the shift towards greener pharmaceutical manufacturing practices.
In conclusion, the incorporation of boronic acid into enzymes represents a significant advancement in organic chemistry. By leveraging directed evolution techniques and an expanded genetic code, researchers have enhanced enzyme efficiency and selectivity for catalysis. This approach holds promise for sustainable drug production through biocatalysis, offering greener alternatives to traditional chemical reactions in the pharmaceutical industry. Continued research and development in this field will lead to the creation of novel enzymes and the optimization of biocatalytic systems for a more sustainable future.
