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A convolutional neural network-based approach for the rapid annotation of molecularly diverse natural products

TitleA convolutional neural network-based approach for the rapid annotation of molecularly diverse natural products
Publication TypeJournal Article
Year of Publication2020
AuthorsReher R., Kim H.W, Zhang C., Mao H.H, Wang M.X, Nothias L.F, Caraballo-Rodriguez A.M, Glukhov E., Teke B., Leao T., Alexander K.L, Duggan BM, Van Everbroeck E.L, Dorrestein PC, Cottrell G.W, Gerwick WH
Date Published2020/03
Type of ArticleArticle
ISBN Number0002-7863
Accession NumberWOS:000518700800007
Keywordsanalog; chemistry; dolastatin 10; drug discovery; marine; swinholide-a

This report describes the first application of the novel NMR-based machine learning tool "Small Molecule Accurate Recognition Technology" (SMART 2.0) for mixture analysis and subsequent accelerated discovery and characterization of new natural products. The concept was applied to the extract of a filamentous marine cyanobacterium known to be a prolific producer of cytotoxic natural products. This environmental Symploca extract was roughly fractionated, and then prioritized and guided by cancer cell cytotoxicity, NMR-based SMART 2.0, and MS2-based molecular networking. This led to the isolation and rapid identification of a new chimeric swinholide-like macrolide, symplocolide A, as well as the annotation of swinholide A, samholides A-I, and several new derivatives. The planar structure of symplocolide A was confirmed to be a structural hybrid between swinholide A and luminaolide B by 1D/2D NMR and LC-MS2 analysis. A second example applies SMART 2.0 to the characterization of structurally novel cyclic peptides, and compares this approach to the recently appearing "atomic sort" method. This study exemplifies the revolutionary potential of combined traditional and deep learning-assisted analytical approaches to overcome longstanding challenges in natural products drug discovery.

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