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.
Bibliographical noteFunding Information:
Supplementary Materials: Supplementary materials can be found at www.mdpi.com/xxx/s1. Author Contributions: Conceptualization, N.M.I., K.S., K.K., L.S. and V.C.; methodology, K.S., R.T., I.B. and J.J.L.M.; data curation, K.S., I.B., S.S., D.E., P.H., L.S. and V.C.; writing—original draft preparation, K.S., N.M.I., I.B., JC.Jo.Ln.cMep.,tRu.aTl.i,zLa.tSio. nan, Nd .VM.C.I..;,wKr.iSt.i,nKg—.Kr.,eLvi.eSw., aanndd Ved.Cit.i;nmg,eKth.So.d, oI.lBo.g, yR,.TK.,.SK.,. KR..,TP..,H I.B, L.,.aSn. adn Jd.MV..;Cd.;astua pceurrvaitsiioonn,, K.S., I.B., S.S., D.E., P.H., L.S., and V.C.; writing—original draft preparation, K.S., N.M.I., I.B., J.M., R.T., L.S., and V.C.; authors read and agreed to the published version of the manuscript. writing—review and editing, K.S., I.B., R.T., K.K., P.H., L.S., and V.C.; supervision, K.S., L.S., and V.C.; project Fadumndininisgt:raTthioisns, tKu.dSy., wK.aKs.s,uLp.Sp.o, artneddVby.Ct.h;eanMdinfuisntrdyinogf Eacdquuciastiitoionn, Y, Kou.Sth., Pan.Hd.,SapnodrtsVo.Cf t.he Czech Republic MSCA IF II project (CZ.02.2.69/0.0/0.0/18_070/0010493) and Czech Science foundation (GACˇ R)—Project No.19-17868Y). This research was also funded by Project “Campania Oncoterapie” No. B61G18000470007. Finally, the study was sMuSpCpoAr tIeFd IIb yprCorjeocsts-(BCoZr.d0e2r.2c.o69o/p0e.0ra/0ti.0o/n18C_z0e7c0h/–0B01a0v4a9r3ia)— anPdroCjezcetcNhoS.c4ie1n. ce foundation (GAČR)—Project No.19-17868Y). This research was also funded by Project “Campania Oncoterapie” No. B61G18000470007. Finally, the Acknowledgments: N.M.I., K.S. and K.K. would like to thank the management of VIT University for providing thestudyfacilitieswas suppto carryortedoutby Crosthis sstu-Bodyrder. cooperation Czech–Bavaria—Project No. 41.
This study was supported by the Ministry of Education, Youth and Sports of the Czech Republic MSCA IF II project (CZ.02.2.69/0.0/0.0/18_070/0010493) and Czech Science foundation (GAČR)—Project No.19-17868Y). This research was also funded by Project “Campania Oncoterapie” No. B61G18000470007. Finally, the study was supported by Cross-Border cooperation Czech–Bavaria—Project No. 41.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
- Biosynthetic gene clusters (BGCs)
- Cyclic dipeptides (2,5-diketopiperazines, DKPs)
- Global natural product social networking (GNPS)
- Natural product
- Quorum sensing inhibition (QSI)
ASJC Scopus subject areas
- Microbiology (medical)