A genetics-free method for high-throughput discovery of cryptic microbial metabolites.

Publication Year
2019

Type

Journal Article
Abstract

Bacteria contain an immense untapped trove of novel secondary metabolites in the form of 'silent' biosynthetic gene clusters (BGCs). These can be identified bioinformatically but are not expressed under normal laboratory growth conditions. Methods to access their products would dramatically expand the pool of bioactive compounds. We report a universal high-throughput method for activating silent BGCs in diverse microorganisms. Our approach relies on elicitor screening to induce the secondary metabolome of a given strain and imaging mass spectrometry to visualize the resulting metabolomes in response to ~500 conditions. Because it does not require challenging genetic, cloning, or culturing procedures, this method can be used with both sequenced and unsequenced bacteria. We demonstrate the power of the approach by applying it to diverse bacteria and report the discovery of nine cryptic metabolites with potentially therapeutic bioactivities, including a new glycopeptide chemotype with potent inhibitory activity against a pathogenic virus.

Journal
Nat Chem Biol
Volume
15
Issue
2
Pages
161-168
Date Published
2019 Feb
ISSN Number
1552-4469
Alternate Journal
Nat Chem Biol
PMCID
PMC6339573
PMID
30617293