Streptomyces are among the most promising genera in terms of production ability to biosynthesize a variety of bioactive secondary metabolites with pharmaceutical interest. Coinciding with the increase in genomic sequencing of these bacteria, mining of their genomes for biosynthetic gene clusters (BGCs) has become a routine component of natural product discovery. Herein, we describe the isolation and characterization of a Streptomyces tendae VITAKN with quorum sensing inhibitory (QSI) activity that was isolated from southern coastal part of India. The nearly complete genome consists of 8,621,231bp with a GC content of 72.2%. Sequence similarity networks of the BGCs detected from this strain against the Minimum Information about a Biosynthetic Gene Cluster (MIBiG) database and 3365 BGCs predicted by antiSMASH analysis of publicly available complete Streptomyces genomes were generated through the BiG-SCAPE-CORASON platform to evaluate its biosynthetic novelty. Crude extract analysis using high-performance liquid chromatography connected to high resolution tandem mass spectrometry (HPLC-HRMS/MS) and dereplication through the Global Natural Product Social Molecular Networking (GNPS) online workflow resulted in the identification of cyclic dipeptides (2, 5-diketopiperazines, DKPs) in the extract, which are known to possess QSI activity. Our results highlight the potential of genome mining coupled with LC-HRMS/MS and in silico tools (GNPS) as a valid approach for the discovery of novel QSI lead compounds. This study also provides the biosynthetic diversity of BGCs and an assessment of the predicted chemical space yet to be discovered.

Department of Biomedical Sciences School of Biosciences and Technology VIT University Vellore 632014 India

Department of Marine Biology Leon H Charney School of Marine Sciences University of Haifa Mt Carmel Haifa 31905 Israel

Department of Ocean Science Division of Life Science and Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory The Hong Kong University of Science and Technology Hong Kong China

Laboratory of Algal Biotechnology Centre Algatech Institute of Microbiology of the Czech Academy of Sciences Opatovickýmlýn Novohradská 237 37981 Třeboň Czech Republic

The Blue Chemistry Lab Dipartimento di Farmacia Università degli Studi di Napoli Federico 2 Via D Montesano 49 80131 Napoli Italy

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Insight into Unprecedented Diversity of Cyanopeptides in Eutrophic Ponds Using an MS/MS Networking Approach