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: Christopher A. Leber, C. Benjamin Naman, Lena Keller, Jehad Almaliti, Eduardo J. E. Caro-Diaz, Evgenia Glukhov, Valsamma Joseph, T. P. Sajeevan, Andres Joshua Reyes, Jason S. Biggs, Te Li, Ye Yuan, Shan He, Xiaojun Yan, William H. Gerwick
Format: Article in Journal/Newspaper
Language:English
Published: MDPI AG 2020
Subjects:
Moorena bouillonii
marine natural products
chemogeography
metabolomics
Biology (General)
QH301-705.5
Indian
Pacific
Orca
Online Access:https://doi.org/10.3390/md18100515
https://doaj.org/article/e68691c31f534a5ca9a3b1ea660216df
Description
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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