Isolation, Genomic and Metabolomic Characterization of <i>Streptomyces tendae</i> VITAKN with Quorum Sensing Inhibitory Activity from Southern India

• Main Authors: Nabila Mohammed Ishaque, Ilia Burgsdorf, Jessie James Limlingan Malit, Subhasish Saha, Roberta Teta, Daniela Ewe, Krishnan Kannabiran, Pavel Hrouzek, Laura Steindler, Valeria Costantino, Kumar Saurav
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Series: Microorganisms
• Subjects: natural product; actinobacteria; quorum sensing inhibition (qsi); biosynthetic gene clusters (bgcs); global natural product social networking (gnps); cyclic dipeptides (2,5-diketopiperazines, dkps); lc-hrms
• Online Access: https://www.mdpi.com/2076-2607/8/1/121

<i>Streptomyces</i> 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 <i>Streptomyces tendae</i> 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 <i>Streptomyces</i> 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.