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Marine microorganisms are receiving more attention as a promising potential source of new natural products. In the present study, we performed genomic and metabolomic analyses to explore the metabolic potential of the obligate marine actinomycete genus Salinispora . The genomes of thirty Salinispora strains were prospected in search of biosynthetic gene clusters including polyketide synthase (PKS), nonribosomal peptide synthetase (NPRS), terpene, indole, lantibiotics, and siderophores. We determined considerable diversity of natural product biosynthetic gene clusters in their genome. There were a total of 1428 putative gene clusters involved in the biosynthesis of various bioactive natural products. Furthermore, 1509 ketosynthase (KS) and condensation (C) domains were detected by using NapDoS belonging to PKS and NRPS genes, respectively. Metabolic profiling was performed by a nontargeted LC-MS/MS approach combined with spectral networking using Global Natural Product Social Molecular Networking (GNPS). Dereplication and tentative identification of natural products were evaluated for common chemical properties and their associated pathways. Significant bioactive natural products such as lomaiviticin C, 7-OH-staurosporine, staurosporine, and cyanosporaside B were determined. More importantly, an unknown glycosylated compound associated with an NRPS/PKS-I hybrid gene cluster in Salinispora pacifica CNY703 was established through chemical and genomic analyses.

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