Discovery and Engineering of Enzymes for Peptide Synthesis and Activation

Enzymes are widely used for peptide synthesis, both for coupling and for terminal activation and modification. Broad-specificity proteases of different mechanistic classes can be used for C-terminal activation and peptide coupling reactions, whereas enzymes that recognize specific sequences are increasingly used for selective modification and tagging. Protein engineering can tailor hydrolases for improved synthesis, better reaction medium tolerance, and desired substrate selectivity. This chapter highlights properties of natural and engineered peptidases, amidases, and peptide transferases for chemoenzymatic peptide synthesis and terminal modification, with an emphasis on basic principles and innovations leading to new applications.