Facile Synthesis of S ‐Substituted L‐Cysteines with Nano‐sized Immobilized O ‐Acetylserine Sulfhydrylase

Many S ‐substituted l ‐cysteines are useful pharmaceutical intermediates but require a simple synthesis method. Here we developed enzymatic synthesis of several S ‐aryl‐ l ‐cysteines and S ‐benzyl‐ l ‐cysteine directly from O ‐acetylserine (OAS) with immobilized O ‐acetylserine sulfhydrylase CysM. Novel iron‐oxide magnetic nanoparticles (MNPs) with cobalt‐nitrilotriacetic acid function were prepared with a diameter of 80 nm in 75 % yield. Direct immobilization of His‐tagged CysM in the cell‐free extract on the MNPs via affinity attachment afforded stable nanobiocatalyst with 97 % enzyme loading efficiency and 93 % free enzyme activity. The immobilized enzyme catalyzed the biotransformation of benzylthiol and OAS to give S ‐benzyl‐ l ‐cysteine in 88 % yield. The nanobiocatalyst also demonstrated high recyclability, retaining 95 % productivity in the fifth cycle. The immobilized CysM accepts various arylthiols to react with OAS, giving rise to a new synthesis route of several S ‐substituted l ‐cysteines in 60–96 % yield.