Metabolomics meets functional assays: coupling LC-MS and microfluidic cell-based receptor-ligand analyses
M G L Henquet1, M Roelse1,2, R C H de Vos1,3
1BU Bioscience, WageningenUR, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
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.
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.
