UC Santa Barbara researchers, led by chemistry professor Yang Yang, have developed a method using photobiocatalysis to produce non-canonical amino acids that are essential building blocks of peptide therapeutics, bioactive natural products, and novel functional proteins. This approach involves using light to excite enzymes, producing energy to convert one molecule into another. By combining the selectivity and efficiency of enzymes with the versatility and sustainability of light, this relatively new field of chemistry opens up new possibilities for creating new processes and molecules, such as non-canonical amino acids.
While most efforts in the field of biocatalysis have focused on optimizing natural enzyme functions or repurposing enzymes for synthetic chemistry, Yang and his team are interested in discovering entirely new enzymatic reactions and modes of enzyme catalysis. By utilizing photobiocatalysis, they were able to develop a triple catalytic cycle involving a photocatalyst and PLP-dependent enzymes, which are responsible for amino acid metabolism. This innovative approach allows for the modification of amino acid substrates through a series of activation steps unique to PLP biochemistry, facilitated by the free radicals generated from photochemistry.
The production of non-canonical amino acids through this process involves altering common amino acid structures to add new features and capabilities. By creating new carbon-carbon bonds to the “alpha carbon” of the amino acid, the researchers can design a range of novel amino acids with unique functions, potentially leading to the development of new therapeutics and natural products. This radical-mediated alpha functionalization of abundant amino acid substrates represents a significant advancement in the field of biocatalysis and opens up new possibilities for synthetic chemistry and enzymology.
In addition to its efficiency, the process is stereoselective, meaning it can select for a preferred three-dimensional shape of the resulting amino acid, eliminating the need for additional steps such as adding and removing protecting groups. The interactions between the photocatalyst and the enzyme are of particular interest to Yang and his team, as they are exploring ways to further improve these interactions for enhanced catalytic efficiency. This research not only contributes to the development of new chemical reactions but also provides insights into fundamental science from both a synthetic chemistry and enzymology standpoint.
Overall, the use of photobiocatalysis to produce non-canonical amino acids represents a significant advancement in the field of biocatalysis and offers new opportunities for creating novel molecules with potential applications in therapeutics and natural products. By leveraging the unique capabilities of enzymes and light, researchers are able to explore new enzymatic reactions and modes of enzyme catalysis, paving the way for further advancements in both synthetic chemistry and enzymology. The innovative methodology developed by the UC Santa Barbara researchers has the potential to drive future research in the field of chemical synthesis and biocatalysis.