Summary Food‐derived peptides are known to possess inhibitory activity against the dipeptidyl‐peptidase IV (DPP‐IV) enzyme, a target in the management of type 2 diabetes. While proteins from commonly consumed food commodities have been investigated as precursors of DPP‐IV‐inhibiting peptides, studies on novel protein sources, such as those from insects, are sparse. This research aimed to determine if DPP‐IV inhibitors can be generated upon in vitro digestion or enzymatic hydrolysis of lesser mealworm protein isolate and concentrate. Treatment of the proteins with digestive enzymes and proteases generated hydrolysates with varying potency, thermolysin being the most effective at releasing active peptides (IC50 = 0.63 and 0.60 mg mL−1 for the isolate and concentrate). Ultrafiltration of the thermolysin‐treated hydrolysates did not significantly improve the potency. This study shows that DPP‐IV inhibitors can be generated from lesser mealworm protein and provides insight on the potential of insects to serve as functional food ingredients.

Bioinformatics was applied for strategic processing of yellow mealworm (Tenebrio molitor) proteins to produce dipeptidyl peptidase (DPP)-IV inhibiting peptides. In silico analysis of 384 mealworm proteins revealed structural proteins as better precursors of DPP-IV inhibiting peptides, compared with other protein types, after pepsin and papain hydrolysis. This was associated with the higher hydropathicity and amounts of residues associated with DPP-IV inhibition in the structural (cuticular) proteins. In silico, the peptides were mostly released with pepsin than papain. Cuticular (CP) and non-cuticular proteins (NC) were extracted from yellow mealworm and hydrolyzed with pepsin and papain in vitro to validate the virtual findings. CP hydrolysate with papain inhibited DPP-IV the most compared to CP hydrolysate with pepsin, whereas NC hydrolysates were mostly inactive. CP had higher hydrophobic-hydrophilic amino acid ratios and contents of the activity-associated residues than NC. The findings demonstrate the application of bioinformatics in processing proteins for bioactive peptide production. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information may be found online in the Supporting Information section.How to cite this article: Dávalos Terán I, Imai K, Lacroix IME, Fogliano V, Udenigwe CC. Bioinformatics of edible yellow mealworm (Tenebrio molitor) proteome reveal the cuticular proteins as promising precursors of dipeptidyl peptidase-IV inhibitors. J Food Biochem. 2020;44:e13121. https ://doi.