Interaction of antidiabetic α-glucosidase inhibitors and gut bacteria α-glucosidase

Carbohydrate hydrolyzing -glucosidases are commonly found in microorganisms present in the human intestine microbiome. We have previously reported crystal structures of an -glucosidase from the human gut bacterium Blaubia (Ruminococcus) obeum (Ro-G1) and its substrate preference/specificity switch. This novel member of the GH31 family is a structural homolog of human intestinal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) with a highly conserved active site that is predicted to be common in Ro-G1 homologs among other species that colonize the human gut. In this report, we present structures of Ro-G1 in complex with the antidiabetic -glucosidase inhibitors voglibose, miglitol, and acarbose and supporting binding data. The in vitro binding of these antidiabetic drugs to Ro-G1 suggests the potential for unintended in vivo crossreaction of the -glucosidase inhibitors to bacterial -glucosidases that are present in gut microorganism communities. Moreover, analysis of these drug-bound enzyme structures could benefit further antidiabetic drug development.