Metabolic profiling as a tool for prioritizing antimicrobial compounds.

Changsheng Wu,Gilles P Van Wezel,Young Hae Choi

doi:10.1007/s10295-015-1666-x

Abstract

Metabolomics is an analytical technique that allows scientists to globally profile low molecular weight metabolites between samples in a medium- or high-throughput environment. Different biological samples are statistically analyzed and correlated to a bioactivity of interest, highlighting differentially produced compounds as potential biomarkers. Here, we review NMR- and MS-based metabolomics as technologies to facilitate the identification of novel antimicrobial natural products from microbial sources. Approaches to elicit the production of poorly expressed (cryptic) molecules are thereby a key to allow statistical analysis of samples to identify bioactive markers, while connection of compounds to their biosynthetic gene cluster is a determining step in elucidating the biosynthetic pathway and allows downstream process optimization and upscaling. The review focuses on approaches built around NMR-based metabolomics, which enables efficient dereplication and guided fractionation of (antimicrobial) compounds.

Highlights

The discovery and development of antibiotics to treat bacterial infections is one of the greatest triumphs of modern medicine
We recently applied nuclear magnetic resonance (NMR)-based metabolomics for the mining of novel soil isolates with promising antibiotic-producing potential, of which we provide a few examples here for illustration purposes
In a time where dereplication is one of the major challenges in screening efforts, metabolomics offers an effective strategy to prioritize novel molecules produced by microorganisms

Summary

Introduction

The discovery and development of antibiotics to treat bacterial infections is one of the greatest triumphs of modern medicine. We discuss ways to enforce fluctuations in the production of bioactive compounds, and the application of metabolomics to facilitate uncovering those compounds, whereby we zoom in on NMR-based metabolic profiling methods, which are less commonly applied in microbial drug discovery.

Results

Conclusion