title: Expanding the Described Metabolome of the Marine Cyanobacterium Moorea producens JHB through Orthogonal Natural Products Workflows.
abstract: Moorea producens JHB, a Jamaican strain of tropical filamentous marine cyanobacteria, has been extensively studied by traditional natural products techniques. These previous bioassay and structure guided isolations led to the discovery of two exciting classes of natural products, hectochlorin (1) and jamaicamides A (2) and B (3). In the current study, mass spectrometry-based 'molecular networking' was used to visualize the metabolome of Moorea producens JHB, and both guided and enhanced the isolation workflow, revealing additional metabolites in these compound classes. Further, we developed additional insight into the metabolic capabilities of this strain by genome sequencing analysis, which subsequently led to the isolation of a compound unrelated to the jamaicamide and hectochlorin families. Another approach involved stimulation of the biosynthesis of a minor jamaicamide metabolite by cultivation in modified media, and provided insights about the underlying biosynthetic machinery as well as preliminary structure-activity information within this structure class. This study demonstrated that these orthogonal approaches are complementary and enrich secondary metabolomic coverage even in an extensively studied bacterial strain.
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, 92093, United States.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Boudreau
authors.affiliation: Department of Biology, William Paterson University, Wayne, New Jersey, 07470, United States of America.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Monroe
authors.affiliation: Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska, 68178, United States of America.
authors.forename: Suneet
authors.initials: S
authors.lastname: Mehrotra
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, 92093, United States; Department of Biology, California State University San Marcos, San Marcos, California, 92078, United States of America.
authors.forename: Shane
authors.initials: S
authors.lastname: Desfor
authors.affiliation: Algorithmic Biology Laboratory, St. Petersburg Academic University, Russian Academy of Sciences, St. Petersburg, 194021, Russia; Department of Mathematics and Mechanics, St. Petersburg State University, St. Petersburg, 194021, Russia; Center for Algorithmic Biotechnology, St. Petersburg State University, St. Petersburg, 194021, Russia.
authors.forename: Anton
authors.initials: A
authors.lastname: Korobeynikov
authors.affiliation: Life Sciences Institute and Department of Medical Chemistry, University of Michigan, Ann Arbor, Michigan, 48109, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Sherman
authors.affiliation: Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska, 68178, United States of America.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Murray
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, 92093, United States.
authors.forename: Lena
authors.initials: L
authors.lastname: Gerwick
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, 92093, United States of America; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, 92093, United States of America.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, 92093, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, 92093, United States of America.
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D000458:Cyanobacteria / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004269:DNA, Bacterial / Q000235:genetics; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D008386:Marine Biology; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D017422:Sequence Analysis, DNA; D057188:Workflow
chemical_list: D001688:Biological Products; D004269:DNA, Bacterial