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Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium .
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
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
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2020-10-14
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Abstract
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 MS1 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 MS2 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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Mar Drugs. 2020 Oct 14;18(10):515. doi: 10.3390/md18100515.
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en
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1660-3397
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Attribution-NonCommercial-ShareAlike 4.0 International