Enhanced dereplication of fungal cultures via use of mass defect filtering

Effective and rapid dereplication is a hallmark of present-day drug discovery from natural sources. This project strove to both decrease the time and expand the structural diversity associated with dereplication methodologies. A 5 min liquid chromatographic run time employing heated electrospray ion...

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Bibliographic Details
Published in:Journal of antibiotics 2017-05, Vol.70 (5), p.553-561
Main Authors: Paguigan, Noemi D, El-Elimat, Tamam, Kao, Diana, Raja, Huzefa A, Pearce, Cedric J, Oberlies, Nicholas H
Format: Article
Language:English
Subjects:
631/326/193
639/638/403/936
Bacteriology
Biological Products - analysis
Biological Products - chemistry
Biomedical and Life Sciences
Bioorganic Chemistry
Chromatography, Liquid - methods
Databases, Factual
Drug Discovery - methods
Fungi - metabolism
Ionization
Life Sciences
Medicinal Chemistry
Metabolites
Microbiology
Organic Chemistry
Original
original-article
Secondary Metabolism
Secondary metabolites
Spectrometry, Mass, Electrospray Ionization - methods
Tandem Mass Spectrometry - methods
Time Factors
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Summary:Effective and rapid dereplication is a hallmark of present-day drug discovery from natural sources. This project strove to both decrease the time and expand the structural diversity associated with dereplication methodologies. A 5 min liquid chromatographic run time employing heated electrospray ionization (HESI) was evaluated to determine whether it could be used as a faster alternative over the 10 min ESI method we reported previously. Results revealed that the 5 min method was as sensitive as the 10 min method and, obviously, was twice as fast. To facilitate dereplication, the retention times, UV absorption maxima, full-scan HRMS and MS/MS were cross-referenced with an in-house database of over 300 fungal secondary metabolites. However, this strategy was dependent upon the makeup of the screening in-house database. Thus, mass defect filtering (MDF) was explored as an additional targeted screening strategy to permit identification of structurally related components. The use of a dereplication platform incorporating the 5 min chromatographic method together with MDF facilitated rapid and effective identification of known compounds and detection of structurally related analogs in extracts of fungal cultures.
ISSN:0021-8820
1881-1469
DOI:10.1038/ja.2016.145