One-Pot Synthesis of Diverse dl-Configuration Dipeptides by a Streptomyces d-Stereospecific Amidohydrolase ▿ †

摘要

The synthesis of diverse dl-configuration dipeptides in a one-pot reaction was demonstrated by using a function of the aminolysis reaction of a d-stereospecific amidohydrolase from Streptomyces sp., a clan SE, S12 family peptidase categorized as a peptidase with d-stereospecificity. The enzyme was able to use various aminoacyl derivatives, including l-aminoacyl derivatives, as acyl donors and acceptors. Investigations of the specificity of the peptide synthetic activity revealed that the enzyme preferentially used d-aminoacyl derivatives as acyl donors. In contrast, l-amino acids and their derivatives were preferentially used as acyl acceptors. Consequently, the synthesized dipeptides had a dl-configuration when d- and l-aminoacyl derivatives were mixed in a one-pot reaction. This report also describes that the enzyme produced cyclo(d–Pro-l-Arg), a specific inhibitor of family 18 chitinase, with a conversion rate for d-Pro benzyl ester and l-Arg methyl ester to cyclo(d-Pro–l-Arg) of greater than 65%. Furthermore, based on results of cyclo(d-Pro–l-Arg) synthesis, we propose a reaction mechanism for cyclo(d-Pro–l-Arg) production.