A homo-FRET assay for patatin-specific proteolytic activity

Food Chem. 2025 Jan 15;463(Pt 1):141105. doi: 10.1016/j.foodchem.2024.141105. Epub 2024 Sep 2.

Abstract

The potato protein patatin embeds bioactive peptides that require targeted hydrolysis to be released as promising food additives. This study presents a patatin-specific protease assay for assessing a wide range of protease activities in high-throughput format. Conjugating patatin to the amine reactive fluorogenic BODIPY FL dye provided a stable protease substrate with efficient homo-FRET quenching at a low degree (7-8) of labeling. Compared to commercial BODIPY-casein, BODIPY-patatin provided higher fluorescence enhancement (by de-quenching) at high protease concentrations, while the sensitivity was generally comparable for both highly specific (e.g. Trypsin) and industrial relevant proteases (e.g. Alcalase and Neutrase) at low doses. For Chymotrypsin, BODIPY-patatin provided a 39 % response improvement at 5 ng dose. A peptide-centric analysis of mass spectrometry-based bottom-up proteomics data identified several BODIPY-labeling sites with varying occupancies in patatin, indicating heterogenous labeling under the applied conjugation conditions. BODIPY-labeled patatin complements commercial BODIPY-labeled casein as a globular, plant-based alternative for screening of proteolytic activity.

Keywords: Assay development; Homo-FRET labeling; Peptide-centric proteomics analysis; Potato protein; Protease screening; Site-specific enrichment analysis.

Publication types

  • Evaluation Study

MeSH terms

  • Enzyme Assays / methods
  • Fluorescence Resonance Energy Transfer
  • Peptide Hydrolases / chemistry
  • Peptide Hydrolases / metabolism
  • Plant Proteins* / chemistry
  • Plant Proteins* / genetics
  • Plant Proteins* / metabolism
  • Proteolysis
  • Solanum tuberosum* / chemistry
  • Solanum tuberosum* / enzymology
  • Solanum tuberosum* / metabolism

Substances

  • Plant Proteins
  • Peptide Hydrolases