Development of advanced chemical biology tools for microbiome metabolism : Chemoselective probes for enhanced metabolomics analysis

• The human microbiome has a profound impact on host physiology by generating highly reactive compounds that can contribute to the development of diseases. These microbial metabolites have a substantial potential that can serve as valuable indicators or biomarkers for different health conditions. Nevertheless, elucidating the microbiota composition and function remains challenging due to its remarkable diversity and complex. Furthermore, conducting a comprehensive analysis of the entire metabolome in a single analytical measurement is difficult. Researchers often employ derivatization techniques in analytical chemistry, which involve modifying the chemical structure of molecules to enhance their detectability, ionization properties and stability during analysis. However, derivatization carries the risk of introducing artifacts or chemical alterations that may compromise the accuracy of analytical results. Consequently, more advanced techniques are urgently required to improve the precision of derivatization-based metabolomics.In response to this challenge, we have developed chemoselective probes immobilized onto magnetic beads to capture metabolites within biological samples. This innovative method improves the mass spectrometric sensitivity by up to a factor of one million, due to the efficient removal of sample matrix background through magnetic separation and improved ionization properties of the metabolites via derivatization. Our approach, termed quant-SCHEMA, has demonstrated the qualitative detection of metabolites containing carbonyl and amine groups with exceptional sensitivity and reproducibility. Additionally, we have successfully applied this method with improved probe design to quantitatively analyse carbonyl-containing metabolites, leading to the discovery of four valuable nutritional biomarkers. Furthermore, we have developed a precise quantification method for short-chain fatty acids (SCFAs) based on this chemoselective probe. The successful implementation of our chemoselective probes highlights the importance of chemical biology tools in advancing metabolomics, which we have termed chemical metabolomics,This comprehensive mass spectrometric analysis expands the horizons of metabolomics-driven biomarker discovery. We envision that our innovative chemical biology tool will find widespread utility in metabolomics analysis, providing valuable insights into microbial interactions with the human host and the development of diseases.

Ämnesord

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

NATURVETENSKAP  -- Kemi -- Analytisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Analytical Chemistry (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

Nyckelord

Chemical biology

Chemoselective modification

Chemical metabolomics

Bioorganic

Microbiome metabolism

Kemi

Chemistry

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