The Tripod for Bacterial Natural Product Discovery: Genome Mining, Silent Pathway Induction, and Mass Spectrometry-Based Molecular Networking.

Daniela B B Trivella,Rafael De Felicio

doi:10.1128/msystems.00160-17

Abstract

Natural products are the richest source of chemical compounds for drug discovery. Particularly, bacterial secondary metabolites are in the spotlight due to advances in genome sequencing and mining, as well as for the potential of biosynthetic pathway manipulation to awake silent (cryptic) gene clusters under laboratory cultivation. Further progress in compound detection, such as the development of the tandem mass spectrometry (MS/MS) molecular networking approach, has contributed to the discovery of novel bacterial natural products. The latter can be applied directly to bacterial crude extracts for identifying and dereplicating known compounds, therefore assisting the prioritization of extracts containing novel natural products, for example. In our opinion, these three approaches-genome mining, silent pathway induction, and MS-based molecular networking-compose the tripod for modern bacterial natural product discovery and will be discussed in this perspective.

Highlights

Natural products are the richest source of chemical compounds for drug discovery
There has been a joint effort of the scientific community to address the bottlenecks in the discovery of new bioactive natural products (NP)
Bacterial secondary metabolites are in the spotlight due to their simple genome organization and to the advances in genome sequencing and mining [3], as well as for their—in theory—facile biosynthetic pathway manipulation and laboratory cultivation [4]

Summary

Introduction

Natural products are the richest source of chemical compounds for drug discovery. bacterial secondary metabolites are in the spotlight due to advances in genome sequencing and mining, as well as for the potential of biosynthetic pathway manipulation to awake silent (cryptic) gene clusters under laboratory cultivation. Genetic or chemical manipulation of microbial growth, and mass spectrometry (MS)-based metabolomics are, in our opinion, the main evolving areas in this field and compose the tripod for modern natural product discovery (Fig. 1). Bacterial secondary metabolites are in the spotlight due to their simple genome organization and to the advances in genome sequencing and mining [3], as well as for their—in theory—facile biosynthetic pathway manipulation and laboratory cultivation [4].

Results

Conclusion