Acarbose glycosylation by AcbE for the production of acarstatins with enhanced α-amylase inhibitory activity.

ABSTRACT: Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties. In this study, we found that AcbE from Actinoplanes sp. SE50/110 catalyzes the production of acarbose analogs that exhibit significantly improved inhibitory activity towards α-amylase than acarbose. Recombinant AcbE mainly catalyzed the formation of two new compounds, namely acarstatins A and B, using acarbose as substrate. Using high-resolution mass spectrometry, nuclear magnetic resonance, and glycosidase hydrolysis, we elucidated their chemical structures as O-α-d-maltosyl-(1 → 4)-acarbose and O-α-d-maltotriosyl-(1 → 4)-acarbose, respectiv

SUBMITTER: Zhang X 

PROVIDER: S-EPMC10981011 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature