Bioprospecting of Limosilactobacillus fermentum Strain MH 2.3 for Anti-diabetic Properties: from Biochemical to Molecular Docking Approaches

Abstract

Diabetes mellitus is a metabolic disorder characterized by an increase in blood glucose beyond normal limits or hyperglycemia due to abnormalities in metabolic processes due to insulin deficiency. Acarbose is now widely used as a drug for people with diabetes mellitus. However, the use of acarbose can cause negative effects in the form of flatulence, diarrhea, and hypoglycemia. Alpha-glucosidase enzyme inhibitors are needed to treat diabetes. Lactic acid bacteria act as inhibitors of alpha-glucosidase activity. This study aimed to determine the presence of specialized metabolites with antidiabetic compounds harvested from Limosilactobacillus fermentum MH 2.3 culture filtrate using biochemical and molecular docking analyses. The use of molecular docking aims to predict ligand bonds and target proteins, which focuses on energy affinity and bond interactions. The results of alpha-glucosidase inhibition assay and molecular docking indicated that L. fermentum MH 2.3 is a prospective “gold mine” in search of novel anti-diabetic compounds. The highest antidiabetic activity, inhibition value of 551.2%, was obtained from the undiluted crude extract of L. fermentum strain MH 2.3 culture following the incubation at 37 ℃ for 72 h. Tert-butyl 3-(1H-tetrazol-5-yl) piperidine-1-carboxylate and benzylmaleimide were found to be the best ligand candidates, as they inhibits the alpha-glucoside activities by forming hydrogen interactions at the leucine residues (734A), similar residues found in its the native ligand. These results are supported by the respective lowest binding energy score of –4.5 kcal/mol when compared with the acarbose as the positive control. The docking was validated by estimating the RMSD values. This finding substantiates the evidence that bioprospecting novel bacterial strains provides a greater chance to discover unknown yet potential bioactive molecules for various biomedical purposes, one of which is a drug candidate to treat diabetic mellitus, which now is considered one of the most life-threatening global epidemics.