What question did this study set out to answer?

The aim is to explore the production of α-glucosidase inhibitory peptides from whey through fermentation and their potential for glycemic management.

February 2, 2026Open Access

Fermentation-Driven Generation of α-Glucosidase Inhibitory Whey Peptides by Marine-Derived Probiotic Lacticaseibacillus casei DS31: Activity Enrichment and Peptidomics

Key Points

The aim is to explore the production of α-glucosidase inhibitory peptides from whey through fermentation and their potential for glycemic management.
Fermentation of whey protein using Lacticaseibacillus casei DS31.
Evaluation of inhibitory activity with IC50 values.
Stepwise purification through ultrafiltration and gel filtration techniques.
Characterization of peptides using LC–MS/MS.
In silico screening and docking for predictive analysis of peptide binding.
Fermentation increased α-glucosidase inhibitory activity significantly.
Crude supernatant showed an IC50 of 2.115 mg/mL, which improved to 1.145 mg/mL after purification.
Nineteen peptides were characterized, with GEPGPEGPAG as a leading candidate based on binding energy predictions.
Molecular docking suggested strong interactions for GEPGPEGPAG with α-glucosidase.

Abstract

This study investigated the generation of α-glucosidase inhibitory peptides from whey protein fermented by the marine-derived probiotic Lacticaseibacillus casei DS31 (isolated from the intestinal microbiota of the large yellow croaker, Larimichthys crocea) and assessed their potential for practical glycemic management. Fermentation markedly increased inhibitory activity, with the freeze-dried crude supernatant exhibiting an IC50 of 2.115 mg/mL. Activity was further enriched through stepwise purification: ultrafiltration (<3 kDa) improved potency (IC50 = 1.206 mg/mL), and subsequent Sephadex (crosslinked dextran) G-15 gel filtration yielded a more active E fraction (IC50 = 1.145 mg/mL). LC–MS/MS characterized 19 peptides, and integrated in silico screening (PeptideRanker combined with molecular docking) highlighted GEPGPEGPAG as a leading candidate, showing a more favorable predicted binding energy (−82.50 kcal/mol) than the positive control acarbose (−69.31 kcal/mol). Docking analysis suggests that GEPGPEGPAG may inhibit α-glucosidase by forming a stable network of hydrogen bonds, salt bridges, and hydrophobic interactions within the catalytic pocket. Overall, DS31-fermented whey and its enriched fractions show promise as functional ingredients for postprandial glycemic control.

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