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Metabolomics meets functional assays: coupling LC-MS and microfluidic cell-based receptor-ligand analyses.

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Summary

This study developed a biosensor combining metabolomics with receptor assays to identify bioactive compounds in chili peppers. The biosensor successfully detected capsaicinoids, linking chemical profiles to biological activity for functional metabolomics.

Keywords:
BioactivityCapsaicinFunctional metabolomicsReceptor-ligand screeningTRPV1

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Analytical Chemistry

Background:

  • Metabolomics provides biochemical profiles but lacks direct bioactivity information.
  • Linking detected compounds to biological activity is crucial for understanding biological processes.
  • Existing metabolomics tools could benefit from methods to directly determine compound bioactivity.

Purpose of the Study:

  • To integrate LC-MS metabolomics with a cell-based receptor assay for enhanced biological understanding.
  • To develop novel opportunities for functional metabolomics by linking chemical and biological data.
  • To identify bioactive compounds in *Capsicum* varieties using a combined approach.

Main Methods:

  • Developed a flow-through biosensor using human cells expressing the TRPV1 receptor and a calcium indicator (YC3.6).
  • Analyzed three *Capsicum* varieties, characterizing compounds using HPLC and high-resolution MS.
  • Utilized the biosensor to correlate individual pepper compounds with TRPV1 receptor activity.

Main Results:

  • Confirmed capsaicin, nordihydrocapsaicin, and dihydrocapsaicin as TRPV1 receptor agonists.
  • Detected receptor activity in *Capsicum* fruit extracts and a commercial product.
  • Biosensor sensitivity to the commercial product matched human sensory thresholds.

Conclusions:

  • The developed TRPV1 biosensor effectively detects bioactive metabolites.
  • This approach offers novel opportunities for functional metabolomics.
  • Directly coupling the biosensor to LC-MS could enable continuous functional assays.