A new aminopeptidase inhibitor from Streptomyces strain HCCB10043 found by UPLC-MS

The diversity of microbial metabolites has been of interest and concern for a long time, yet a suitable method for discovering these is still unavailable. In the work discussed in this report, ultra-performance liquid chromatography coupled with tandem quadrupole and time of flight high-resolution mass spectrometry (UPLC-Q-TOF-HRMS), with MS data analysis, was set up to study the metabolites of Streptomyces strain HCCB10043. It was found that besides antibacterial substances (A21978C complex) and two anti-aminopeptidase compounds (valistatin and bestatin), this strain can produce a new aminopeptidase inhibitor, identified as 3-amino-2-hydroxy-4-phenylbutanoylvalylisoleucine. This new compound had greater activity than valistatin or bestatin in aminopeptidase N (APN) inhibition assay. The results proved that combination of UPLC-Q-TOF-MS analysis and classic purification and identification steps as complementary strategies can provide a method with high reliability for research on microbial secondary metabolites. Furthermore, it has shown that the study of secondary metabolic profiling might be the key to discovering new drugs.