From Synthesis of Amino Acids and Peptides to Enzymatic Catalysis: A Bottom‐Up Approach in Mechanochemistry

Recently, chemical reactions induced or facilitated by mechanical energy have gained recognition in diverse areas of chemical synthesis. In particular, mechanosyntheses of amino acids and short peptides, along with their applications in catalysis, have revealed the high degree of stability of peptide bonds in environments of harsh mechanical stress. These observations quickly led to the recent interest in developing mechanochemical enzymatic reactions. Experimentally, manual grinding, ball‐milling techniques, and twin‐screw extrusion technology have proven valuable to convey mechanical forces into a chemical synthesis. These practices have enabled the establishment of more sustainable alternatives for chemical synthesis by reducing the use of organic solvents and waste production, thereby having a direct impact on the E‐factor of the chemical process. In this Minireview, the series of events that allowed the development of mechanochemical enzymatic reactions are described from a bottom‐up perspective. Starting from the bottom: Progressively, mechanochemical techniques such as grinding, ball‐milling, and twin‐screw extrusion have been successfully utilized for the synthesis of amino acids, peptides, and recently to develop mechanoenzymatic reactions in a more sustainable manner.