A Metabolomics-Based Toolbox to Assess and Compare the Metabolic Potential of Unexplored, Difficult-to-Grow Bacteria

authored by

Federica Fiorini, Felizitas Bajerski, Olga Jeske, Cendrella Lepleux, Jörg Overmann, Mark Brönstrup

Abstract

Novel high-throughput cultivation techniques create a demand to pre-select strains for in-depth follow-up studies. We report a workflow to identify promising producers of novel natural products by systematically characterizing their metabolomes. For this purpose, 60 strains from four phyla (Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes) comprising 16 novel species and six novel genera were cultivated from marine and terrestrial sources. Their cellular metabolomes were recorded by LC-MS/MS; data analysis comprised databases MS/MS matching, in silico compound assignment, and GNPS-based molecular networking. Overall, 1052 different molecules were identified from 6418 features, among them were unusual metabolites such as 4-methoxychalcone. Only a minor portion of the 755 features were found in all phyla, while the majority occurred in a single phylogroup or even in a single strain. Metabolomic methods enabled the recognition of highly talented strains such as AEG42_45, which had 107 unique features, among which a family of 28 potentially novel and related compounds according to MS/MS similarities. In summary, we propose that high-throughput cultivation and isolation of bacteria in combination with the presented systematic and unbiased metabolome analysis workflow is a promising approach to capture and assess the enormous metabolic potential of previously uncultured bacteria.

Organisation(s)

Centre of Biomolecular Drug Research (BMWZ)

External Organisation(s)

Helmholtz Centre for Infection Research (HZI)
Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures
Technische Universität Braunschweig
German Center for Infection Research (DZIF)

Type

Article

Journal

Marine Drugs

Volume

20

No. of pages

22

ISSN

1660-3397

Publication date

11.2022

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Pharmaceutical Science, Drug Discovery, Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Sustainable Development Goals

SDG 14 - Life Below Water

Electronic version(s)

https://doi.org/10.3390/md20110713 (Access: Open)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698959/ (Access: Open)