LC-HRMS-database screening metrics for rapid prioritization of samples to accelerate the discovery of structurally new natural products

Tabudravu, J. N. et al. (2019) LC-HRMS-database screening metrics for rapid prioritization of samples to accelerate the discovery of structurally new natural products. Journal of Natural Products, 82(2), pp. 211-220. (doi: 10.1021/acs.jnatprod.8b00575) (PMID:30735391)

Abstract

In 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.

• Item Type: Articles
• Additional Information: The research leading to these results received funding from the European Union’s Seventh Framework Programme (FP7/ 2007-2013) under grant agreement no. 312184 “PharmaSea” to M.J., R.E., J.T., H.D., R.K., and G.C. B.F.M. thanks the Laboratory for Advanced Computing (LCA) of the University of Coimbra for computing time, and the Portuguese Foundation for Science and Tehnology for financial support under project POCI-01-0145-FEDER032229.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kelly, Dr Sharon
• Authors: Tabudravu, J. N., Pellissier, L., Smith, A. J., Subko, K., Autréau, C., Feussner, K., Hardy, D., Butler, D., Kidd, R., Milton, E. J., Deng, H., Ebel, R., Salonna, M., Gissi, C., Montesanto, F., Kelly, S. M., Milne, B. F., Cimpan, G., and Jaspars, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Journal of Natural Products
• Publisher: American Chemical Society
• ISSN: 0163-3864
• ISSN (Online): 1520-6025
• Published Online: 08 February 2019
• Copyright Holders: Copyright © 2019 American Chemical Society and American Society of Pharmacognosy
• First Published: First published in Journal of Natural Products 82(2): 211-220
• Publisher Policy: Reproduced in accordance with the publisher copyright policy