Newly Developed Technique Unveiled by Scientists for Non-Canonical Amino Acid Synthesis with Enhanced Synergy

In a groundbreaking development, researchers at UC Santa Barbara have combined the power of enzymes with small-molecule photochemistry to create a synergistic method for catalytic reactions. This new approach has the potential to revolutionize the synthesis of non-canonical amino acids, which are crucial for therapeutic purposes.

“This method solves what in my opinion is one of the most important problems in our field: how to develop new catalytic reactions in a general sense that are new to both biology and chemistry,” said chemistry Professor Yang Yang, an author of a paper published in the journal Science. “On top of that, the process is stereoselective, meaning it can select for a preferred shape of the resulting amino acid.”

The synergistic photobiocatalytic method combines two co-occurring reactions. The photochemical reaction produces an intermediate molecule that works together with the reactive intermediate of the enzymatic process to produce the amino acid.

On one side, an enzyme activates a natural amino acid substrate and forms an enzymatic intermediate. On the other side, a small molecule photocatalyst absorbs visible light to activate another substrate, producing a short-lived radical species. The lab’s innovation lies in the intermediate molecule generated by the enzymatic reaction, which captures the radical.

The captured radical reacts with the enzymatically formed intermediate, enabling efficient stereochemical reactions. This efficient process simplifies the synthesis of non-canonical amino acids, reducing the number of steps by three to five compared to conventional methods.

The Yang Lab’s breakthrough could have significant implications for peptide therapies, as it provides a selective and streamlined approach to amino acid synthesis. Furthermore, this method opens possibilities for exploring new reactions and accessing previously unattainable compounds.

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