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.
Malaria is a major public health concern, and malarial parasites have developed resistance against the commonly available drugs. So now a days it is a major concern to find out a new target for drug therapy. Plasmodium falciparum 3D7, one of the strains of plasmodium species also lacks in a functional tricarboxylic acid cycle and solely dependent on glycolysis for its energy supply like other plasmodium species. Although enzymes of malarial parasite have been considered as potential antimalarial drug targets, a little is known about their structural biology. The tertiary structure of triose phosphate isomerase of P. falciparum 3D7 was determined by means of homology modeling through multiple alignment followed by intensive optimization and validation. The modeling was done by Swiss-Model Workspace. The obtained model was verified with the structure validation programs such as, PROCHECK, Verify3D, and QMEAN for reliability. The verify3D value of 0.69 indicates that the environment profile of the model is good. A self-optimized prediction method with alignment or SOPMA is employed for calculation of the secondary structural features of triose phosphate isomerase. The secondary structure indicates that the predicted 3D structure of triosephosphate isomerase of P. falciparum 3D7 contains 48.37% α-helix, 29.27% random coil, and 16.67% extended strand. Active site determination through CASTp suggests that this protein can be utilized as a potential drug target. However, these will further be tested by wet lab studies for a targeted vaccine design against P. falciparum 3D7.
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