Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium Moorena bouillonii

The tropical marine cyanobacterium Moorena bouillonii occupies a large geographic range across the Indian and Western Tropical Pacific Oceans and is a prolific producer of structurally unique and biologically active natural products. An ensemble of computational approaches, including the creation of...

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Bibliographic Details
Published in:Marine Drugs
Main Authors: Leber, Christopher A., Naman, C. Benjamin, Keller, Lena, Almaliti, Jehad, Caro-Diaz, Eduardo J. E., Glukhov, Evgenia, Joseph, Valsamma, Sajeevan, T. P., Reyes, Andres Joshua, Biggs, Jason S., Li, Te, Yuan, Ye, He, Shan, Yan, Xiaojun, Gerwick, William H.
Format: Text
Language:English
Published: MDPI 2020
Subjects:
Article
Indian
Pacific
Orca
Online Access:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602127/
http://www.ncbi.nlm.nih.gov/pubmed/33066480
https://doi.org/10.3390/md18100515
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Summary:The tropical marine cyanobacterium Moorena bouillonii occupies a large geographic range across the Indian and Western Tropical Pacific Oceans and is a prolific producer of structurally unique and biologically active natural products. An ensemble of computational approaches, including the creation of the ORCA (Objective Relational Comparative Analysis) pipeline for flexible MS(1) feature detection and multivariate analyses, were used to analyze various M. bouillonii samples. The observed chemogeographic patterns suggested the production of regionally specific natural products by M. bouillonii. Analyzing the drivers of these chemogeographic patterns allowed for the identification, targeted isolation, and structure elucidation of a regionally specific natural product, doscadenamide A (1). Analyses of MS(2) fragmentation patterns further revealed this natural product to be part of an extensive family of herein annotated, proposed natural structural analogs (doscadenamides B–J, 2–10); the ensemble of structures reflect a combinatorial biosynthesis using nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) components. Compound 1 displayed synergistic in vitro cancer cell cytotoxicity when administered with lipopolysaccharide (LPS). These discoveries illustrate the utility in leveraging chemogeographic patterns for prioritizing natural product discovery efforts.

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