# Leveraging chemical synthesis to discover metabolites from the gut microbiome

## TL;DR

This paper reviews how chemical synthesis helps identify bioactive metabolites from gut microbes, which could have medicinal uses.

## Contribution

The paper highlights novel uses of chemical synthesis in combination with metabolomics and genomics to discover new gut microbiome metabolites.

## Key findings

- Chemical synthesis validates structures of gut microbial metabolites when traditional isolation is not feasible.
- Next-generation workflows integrate synthesis with metabolomic and genomic data to uncover new bioactive molecules.
- Synthetic chemistry is essential for biological testing of newly discovered metabolites.

## Abstract

The gut microbiome has the biosynthetic potential to make a variety of secondary metabolites or natural products, which serve as molecular messages between cells and organisms. These chemical signals are capable of affecting physiology and behavior in real time, and are, therefore, bioactive and can exhibit medicinal properties including anticancer, antimicrobial, or immunomodulating activities. It is clearly important to identify signaling molecules in the human gut, but elucidating their chemical structures can be challenging since traditional isolation methods are typically not available. The discovery of microbiome‐related metabolites requires multidisciplinary collaboration, where chemical synthesis often plays an essential role. This review highlights examples where synthetic chemistry was used to study novel metabolites produced by the gut microbiota. In the first part, we describe examples where organic synthesis was utilized in traditional contexts, as a last step for validating structures and sourcing material for biological testing. The final section of this review discusses next‐generation applications for chemical synthesis, where integration with metabolomic or genomic analysis simultaneously uncovers both structural and biological information about small molecules from the gut.

Metabolomics or the study of small molecule metabolism is used to identify compounds produced by the gut microbiota, but chemical annotation is a major bottleneck. Here, we review examples where organic synthesis was leveraged in traditional or next generation workflows to help identify new bioactive gut microbial metabolites.