The importance of mass spectrometric dereplication in fungal secondary metabolite analysis

Kristian Fog Nielsen, Thomas Ostenfeld Larsen

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    Abstract

    Having entered the Genomic Era, it is now evident that the biosynthetic potential of filamentous fungi is much larger than was thought even a decade ago. Fungi harbor many cryptic gene clusters encoding for the biosynthesis of polyketides, non-ribosomal peptides, and terpenoids - which can all undergo extensive modifications by tailoring enzymes - thus potentially providing a large array of products from a single pathway. Elucidating the full chemical profile of a fungal species is a challenging exercise, even with elemental composition provided by high-resolution mass spectrometry (HRMS) used in combination with chemical databases (e.g., AntiBase) to dereplicate known compounds. This has led to a continuous effort to improve chromatographic separation in conjunction with improvement in HRMS detection. Major improvements have also occurred with 2D chromatography, ion-mobility, MS/MS and MS3, stable isotope labeling feeding experiments, classic UV/Vis, and especially automated data-mining and metabolomics software approaches as the sheer amount of data generated is now the major challenge. This review will focus on the development and implementation of dereplication strategies and will highlight the importance of each stage of the process from sample preparation to chromatographic separation and finally toward both manual and more targeted methods for automated dereplication of fungal natural products using state-of-the art MS instrumentation.
    Original languageEnglish
    Article number71
    JournalFrontiers in Microbiology
    Volume6
    Number of pages15
    ISSN1664-302X
    DOIs
    Publication statusPublished - 2015

    Bibliographical note

    Copyright © 2015 Nielsen and Larsen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    Keywords

    • elemental composition
    • polyketide
    • 10060, Biochemistry studies - General
    • diode array detection laboratory techniques
    • fungal secondary metabolite analysis laboratory techniques
    • high-resolution mass spectrometry laboratory techniques
    • mass spectrometry laboratory techniques, spectrum analysis techniques
    • two-dimensional chromatography laboratory techniques, chromatographic techniques
    • Biochemistry and Molecular Biophysics
    • Methods and Techniques
    • MICROBIOLOGY
    • HYDROPHILIC INTERACTION CHROMATOGRAPHY
    • PERFORMANCE LIQUID-CHROMATOGRAPHY
    • INTER-LABORATORY TRANSFERABILITY
    • NATURAL-PRODUCT EXTRACTS
    • ELECTROSPRAY-IONIZATION
    • ASPERGILLUS-NIDULANS
    • STABLE-ISOTOPE
    • REVERSED-PHASE
    • ANION-EXCHANGE
    • ION-TRAP
    • liquid chromatography
    • metabolomics
    • mass spectrometry
    • diode array detection
    • dereplication

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