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LC-HRMS-Database Screening Metrics for Rapid Prioritization of Samples to Accelerate the Discovery of Structurally New Natural Products
journal contribution
posted on 2019-02-08, 19:10 authored by Jioji N. Tabudravu, Léonie Pellissier, Alan James Smith, Karolina Subko, Caroline Autréau, Klaus Feussner, David Hardy, Daniel Butler, Richard Kidd, Edward J. Milton, Hai Deng, Rainer Ebel, Marika Salonna, Carmela Gissi, Federica Montesanto, Sharon M. Kelly, Bruce F. Milne, Gabriela Cimpan, Marcel JasparsIn order to accelerate the isolation
and characterization of structurally
new or novel secondary metabolites, it is crucial to develop efficient
strategies that prioritize samples with greatest promise early in
the workflow so that resources can be utilized in a more efficient
and cost-effective manner. We have developed a metrics-based prioritization
approach using exact LC-HRMS, which uses data for 24 618 marine
natural products held in the PharmaSea database. Each sample was evaluated
and allocated a metric score by a software algorithm based on the
ratio of new masses over the total (sample novelty), ratio of known
masses over the total (chemical novelty), number of peaks above a
defined peak area threshold (sample complexity), and peak area (sample
diversity). Samples were then ranked and prioritized based on these
metric scores. To validate the approach, eight marine sponges and
six tunicate samples collected from the Fiji Islands were analyzed,
metric scores calculated, and samples targeted for isolation and characterization
of new compounds. Structures of new compounds were elucidated by spectroscopic
techniques, including 1D and 2D NMR, MS, and MS/MS. Structures were
confirmed by computer-assisted structure elucidation methods (CASE)
using the ACD/Structure Elucidator Suite.
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tunicate samplesprioritize samplessoftware algorithmLC-HRMS-Database Screening MetricsscorePharmaSea databasespectroscopic techniquesStructurally New Natural Products2 D NMRmetrics-based prioritization approachACD24 618 marine1 DFiji Islandsmarine spongesstructure elucidation methodssample diversitypeak area24 618peak area thresholdRapid Prioritization
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