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Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products

Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products

Published on: March 12, 2020

Genome mining for methanobactins.

Grace E Kenney¹, Amy C Rosenzweig

¹Departments of Molecular Biosciences and of Chemistry, Northwestern University, Evanston, IL 60208, USA.

|February 28, 2013

Summary

This summary is machine-generated.

Methanobactins (Mbns), copper-binding compounds, are found in more bacterial species than previously known, suggesting a wider role in metal homeostasis. This study links precursor peptide sequences to Mbn structure, aiding in the discovery of new Mbns and their biosynthetic pathways.

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Targeted DNA Methylation Analysis by Next-generation Sequencing

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Published on: February 24, 2015

Area of Science:

Microbiology
Biochemistry
Genomics

Background:

Methanobactins (Mbns) are copper-binding natural products essential for copper uptake in methanotrophic bacteria.
Known Mbns feature copper coordinated by nitrogen heterocycles and thioamide groups within a peptide backbone.
The genetic basis and broader distribution of Mbn biosynthesis remain largely unexplored.

Purpose of the Study:

To investigate the prevalence and genetic basis of methanobactin production across diverse bacterial species.
To identify novel genes and pathways involved in Mbn biosynthesis and transport.
To establish structure-function relationships between Mbn precursor peptides and final Mbn structures.

Main Methods:

Genome mining of microbial databases to identify Mbn precursor peptides (MbnAs) and associated genes.
Bioinformatic analysis of operon structures and protein sequences to classify Mbn biosynthesis clusters.
Comparative genomics to identify conserved and variable elements in Mbn biosynthetic pathways.

Main Results:

Operons encoding MbnA, MbnB, and MbnC were identified in 16 new bacterial species, including non-methanotrophs.
Species were categorized into five groups based on operon composition, revealing diverse biosynthetic strategies.
Conserved transporters (MATE, TonB-dependent) and novel proteins (di-heme cytochrome c peroxidase) were identified, alongside various modifying enzymes.

Conclusions:

Mbn-like compounds are more widespread than previously assumed, extending beyond methanotrophs and indicating a broader role in metal homeostasis.
The study establishes a link between Mbn precursor peptide sequence and Mbn structure, enabling prediction of novel Mbn variants.
Emerging models for Mbn transport and copper regulation, along with the potential for novel chemistry discovery, are highlighted.