• DIPTI SAREEN

      Articles written in Journal of Biosciences

    • Non-ribosomal peptide synthetases: Identifying the cryptic gene clusters and decoding the natural product

      MANGAL SINGH SANDEEP CHAUDHARY DIPTI SAREEN

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      Non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) present in bacteria and fungi are themajor multi-modular enzyme complexes which synthesize secondary metabolites like the pharmacologically importantantibiotics and siderophores. Each of the multiple modules of an NRPS activates a different amino or aryl acid,followed by their condensation to synthesize a linear or cyclic natural product. The studies on NRPS domains, theknowledge of their gene cluster architecture and tailoring enzymes have helped in the in silico genetic screening of theever-expanding sequenced microbial genomic data for the identification of novel NRPS/PKS clusters and thusdeciphering novel non-ribosomal peptides (NRPs). Adenylation domain is an integral part of the NRPSs and is thesubstrate selecting unit for the final assembled NRP. In some cases, it also requires a small protein, the MbtHhomolog, for its optimum activity. The presence of putative adenylation domain and MbtH homologs in a sequencedgenome can help identify the novel secondary metabolite producers. The role of the adenylation domain in the NRPSgene clusters and its characterization as a tool for the discovery of novel cryptic NRPS gene clusters are discussed.

    • Thiopeptides encoding biosynthetic gene clusters mined from bacterial genomes

      ESHANI AGGARWAL SRISHTI CHAUHAN DIPTI SAREEN

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      Currently, we are at the threshold of the ‘post-antibiotic era’ due to the global emergence of antimicrobialresistance (AMR), and hence there is a dire need to discover new antibiotics. Ribosomally synthesized andpost-translationally modified peptides (RiPPs) are a diverse class of natural products (NPs), some of which areunder clinical trials for their antimicrobial potential. Thiopeptides are structurally one of the most complexclasses of RiPPs due to numerous post-translational modifications (PTMs), with [4?2] cycloaddition being thecore PTM and are active against several gram-positive pathogens. Genome mining coupled with experimentalwork can harness the unexplored ‘cryptic’ gene clusters while minimizing the rate of the rediscovery of knownmetabolites and expand the molecular diversity of NPs with medicinal potential. Employing the genomemining approach using a series of freely available bioinformatics tools, we have identified eight novel putativethiopeptide encoding biosynthetic gene clusters (BGCs) from different bacterial genomes, most of whichbelong to the class Actinobacteria. Our results provide confidence in the newly identified BGCs, to proceedwith wet-bench experiments and discover novel thiopeptide(s).

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