Isolation and characterization of peptides with dipeptidyl peptidase IV (DPPIV) inhibitory activity from natto using DPPIV from Aspergillus oryzae

Human-derived dipeptidyl peptidase IV (DPPIV) is a costly material used in the discovery of drugs for diabetes. In this study, we demonstrated the efficacy of DPPIV from Aspergillus oryzae as an alternative to human-derived DPPIV for identifying DPPIV inhibitors. Fermented soybean, also called natto, suppresses blood glucose levels in humans; however, the underlying mechanism remains unknown. This study determined the in vitro DPPIV inhibitory activity of isolated peptides from natto. Amino acid sequences of two peptides isolated from natto were identified by LC/MS/MS as Lys-Leu and Leu-Arg. These isolated peptides inhibited DPPIV in a dose-dependent manner, with IC50 values of 41.40 ± 2.68 and 598.02 ± 18.35 μg/ml, respectively. These results indicate the potential mechanism of blood glucose control by natto and novel roles of Lys-Leu and Leu-Arg as DPPIV inhibitors.