Combining mass spectrometric metabolic profiling with genomic analysis: A powerful approach for discovering natural products from cyanobacteria

TitleCombining mass spectrometric metabolic profiling with genomic analysis: A powerful approach for discovering natural products from cyanobacteria
Publication TypeJournal Article
Year of Publication2015
AuthorsKleigrewe K., Almaliti J., Tian I.Y, Kinnel R.B, Korobeynikov A., Monroe E.A, Duggan BM, Di Marzo V., Sherman D.H, Dorrestein PC, Gerwick L, Gerwick WH
JournalJournal of Natural Products
Volume78
Pagination1671-1682
Date Published2015/07
Type of ArticleArticle
ISBN Number0163-3864
Accession NumberWOS:000358700000025
Keywordsbarbamide biosynthesis; biosynthetic gene-cluster; cannabinoid receptors; curacin-a; in-vitro; lyngbya-majuscula; marine cyanobacterium; molecular networking; polyketide; Secondary metabolites
Abstract

An innovative approach was developed for the discovery of new natural products by combining mass spectrometric metabolic profiling with genomic analysis and resulted in the discovery of the columbamides, a new class of di- and trichlorinated acyl amides with cannabinomimetic activity. Three species of cultured marine cyanobacteria, Moorea producens 3L, Moorea producens JHB, and Moorea bouillonii PNG, were subjected to genome sequencing and analysis for their recognizable biosynthetic pathways, and this information was then compared with their respective metabolomes as detected by MS profiling. By genome analysis, a presumed regulatory domain was identified upstream of several previously described biosynthetic gene clusters in two of these cyanobacteria, M. producens 3L and M producens JHB. A similar regulatory domain was identified in the M. bouillonii PNG genome, and a corresponding downstream biosynthetic gene cluster was located and carefully analyzed. Subsequently, MS-based molecular networking identified a series of candidate products, and these were isolated and their structures rigorously established. On the basis of their distinctive acyl amide structure, the most prevalent metabolite was evaluated for cannabinomimetic properties and found to be moderate affinity ligands for CB1.

DOI10.1021/acs.jnatprod.5b00301
Short TitleJ. Nat. Prod.
Student Publication: 
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Research Topics: 
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