Chlorinated metabolites from <i>Streptomyces</i> sp. highlight the role of biosynthetic mosaics and superclusters in the evolution of chemical diversity

Morshed, M. T.; Lacey, Ernest; Vuong, Daniel; Lacey, Alastair E.; Lean, Soo-Sum; Moggach, Stephen A.; Karuso, Peter; Chooi, Yit‐Heng; Booth, Thomas; Piggott, Andrew M.

doi:10.1039/d1ob00600b

Cited by 11 publications

(12 citation statements)

References 114 publications

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“…Furthermore, recent studies highlighted a high biodiversity of natural products, including anthrabenzoxocinone compounds, produced by bacteria isolated from natural habitats [32], and a high genetic potential of Streptomyces spp. in production of a variety of bioactive compounds, also including anthrabenzoxocinones [33]. Our results, presented in this report, corroborate these conclusions.…”

Section: Discussionsupporting

confidence: 90%

Antibacterial, Antifungal and Anticancer Activities of Compounds Produced by Newly Isolated Streptomyces Strains from the Szczelina Chochołowska Cave (Tatra Mountains, Poland)

et al. 2021

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Resistance of bacteria, fungi and cancer cells to antibiotics and other drugs is recognized as one of the major problems in current medicine. Therefore, a search for new biologically active compounds able to either kill pathogenic cells or inhibit their growth is mandatory. Hard-to-reach habitats appear to be unexplored sources of microorganisms producing previously unknown antibiotics and other molecules revealing potentially therapeutic properties. Caves belong to such habitats, and Actinobacteria are a predominant group of microorganisms occurring there. This group of bacteria are known for production of many antibiotics and other bioactive compounds. Interestingly, it was demonstrated previously that infection with bacteriophages might enhance production of antibiotics by them. Here, we describe a series of newly isolated strains of Actinobacteria that were found in caves from the Tatra Mountains (Poland). Phage induction tests indicated that some of them may bear active prophages able to produce virions upon treatment with mitomycin C or UV irradiation. Among all the examined bacteria, two newly isolated Streptomyces sp. strains were further characterized to demonstrate their ability to inhibit the growth of pathogenic bacteria (strains of Staphylococcus aureus, Salmonella enterica, Enterococcus sp., Escherichia coli, and Pseudomonas aeruginosa) and fungi (different species and strains from the genus Candida). Moreover, extracts from these Streptomyces strains reduced viability of the breast-cancer cell line T47D. Chemical analyses of these extracts indicated the presence of isomers of dichloranthrabenzoxocinone and 4,10- or 10,12-dichloro-3-O-methylanthrabenzoxocinone, which are putative antimicrobial compounds. Moreover, various previously unknown (unclassified) molecules were also detected using liquid chromatography–mass spectrometry, suggesting that tested Streptomyces strains may synthesize a battery of bioactive compounds with antibacterial, antifungal, and anticancer activities. These results indicate that further studies on the newly isolated Actinobacteria might be a promising approach to develop novel antibacterial, antifungal, and/or anticancer drugs.

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Section: Discussionsupporting

confidence: 90%

Antibacterial, Antifungal and Anticancer Activities of Compounds Produced by Newly Isolated Streptomyces Strains from the Szczelina Chochołowska Cave (Tatra Mountains, Poland)

et al. 2021

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“…In summary, cblaster can uncover homologous gene clusters and evolutionary relationships at a pace that far exceeds other available software and has become an indispensable tool in both our own research into the BGCs of fungi and bacteria ( Lacey et al , 2019 ; Li et al , 2019 , 2020 , 2021 ; Morshed et al , 2021 ) and in others ( Jung et al , 2021 ; Williams et al , 2021 ). We foresee cblaster being used to uncover novel variants of known pathways, or to prospect for new combinations of biological parts for use in synthetic biology ( Gilchrist et al , 2018 ; Sun et al , 2015 ; Wang et al , 2013 ).…”

Section: New Approaches and Practical Applicationsmentioning

confidence: 99%

cblaster: a remote search tool for rapid identification and visualization of homologous gene clusters

Gilchrist

Booth

Wersch

et al. 2021

Bioinformatics Advances

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153

126

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Motivation Genes involved in coordinated biological pathways, including metabolism, drug resistance and virulence, are often collocalised as gene clusters. Identifying homologous gene clusters aids in the study of their function and evolution, however existing tools are limited to searching local sequence databases. Tools for remotely searching public databases are necessary to keep pace with the rapid growth of online genomic data. Results Here, we present cblaster, a Python based tool to rapidly detect collocated genes in local and remote databases. cblaster is easy to use, offering both a command line and a user-friendly graphical user interface (GUI). It generates outputs that enable intuitive visualisations of large datasets, and can be readily incorporated into larger bioinformatic pipelines. cblaster is a significant update to the comparative genomics toolbox. Availability cblaster source code and documentation is freely available from GitHub under the MIT license (github.com/gamcil/cblaster). Supplementary information Supplementary data are available at Bioinformatics Advances online.

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“…[26][27][28][29][30][31] We have recently highlighted the importance of biosynthetic sub-clusters in the evolution of biosynthesis. 24 The utilisation of the DPG synthase in the biosynthesis of hybrid peptides and polyketides, like the resorculins, is another elegant example of this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently demonstrated the power of biosynthetic subclusters to rapidly annotate BGCs. 24 Analysis of the putative resorculin (rsn) BGC with cblaster 25 identified conserved genes for the biosynthesis and incorporation of 3,5-DHPGO (Fig. 3/ Table S5 †).…”

Section: Resorculin Biosynthesismentioning

confidence: 99%

Resorculins: hybrid polyketide macrolides from Streptomyces sp. MST-91080

Chen¹,

Vuong²,

Lacey

et al. 2023

Org. Biomol. Chem.

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Chlorinated metabolites from Streptomyces sp. highlight the role of biosynthetic mosaics and superclusters in the evolution of chemical diversity

Abstract: LCMS-guided screening of a library of biosynthetically talented bacteria and fungi identified Streptomyces sp. MST-144321 as a prolific producer of chlorinated metabolites. We isolated and characterised six new and nine...

Cited by 11 publications

References 114 publications

Antibacterial, Antifungal and Anticancer Activities of Compounds Produced by Newly Isolated Streptomyces Strains from the Szczelina Chochołowska Cave (Tatra Mountains, Poland)

Antibacterial, Antifungal and Anticancer Activities of Compounds Produced by Newly Isolated Streptomyces Strains from the Szczelina Chochołowska Cave (Tatra Mountains, Poland)

cblaster: a remote search tool for rapid identification and visualization of homologous gene clusters

Resorculins: hybrid polyketide macrolides from Streptomyces sp. MST-91080

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