Enzyme Engineering for High‐Yielding Amide Formation: Lipase‐Catalyzed Synthesis of <i>N</i> ‐Acyl Glycines in Aqueous Media

Amide syntheses remain a key challenging green chemistry reaction. For instance, synthesis of N-acyl glycines as biosurfactants and therapeutics is highly desirable to replace chemical pathways using toxic phosgene. Herein, we report novel concept for enzymatic amidation in an aqueous system via glycerol activation fatty acids theirsubsequent aminolysis with glycine synthesize glycines. We then engineer enzyme (proRML) by reshaping its catalytic pocket enhance activity efficiency 103-fold 465-fold, respectively. The evolved proRML (D156S/L258K/L267N/S83D/L58K/R86K/W88V) catalyzed the acid give N-lauroylglycine high yield (80 %). It accepts broad range medium- long-chain (C8–C18), giving yields N-decanoyl-, N-myristoyl-, N-oleoylglycine. developed may be general, engineered useful