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Bioprospecting of Actinobacterial Diversity and Antibacterial Secondary Metabolites from the Sediments of Four Saline Lakes on the Northern Tibetan Plateau. | LitMetric

AI Article Synopsis

  • The Tibetan Plateau, also called the "Roof of the World", contains saline lakes that are sparsely studied due to harsh environmental conditions, particularly focusing on actinobacteria from these lakes.
  • In this study, researchers isolated 255 actinobacterial strains and evaluated their potential antibacterial properties, discovering 46 strains that showed activity against pathogens, including two strains that caused DNA damage.
  • Advanced techniques like metabolomics profiling revealed three bioactive metabolites (cosmomycin, kidamycin, and hedamycin) and indicated the presence of novel anthracycline compounds, showcasing the effectiveness of combining genomics and metabolomics for identifying valuable microbial chemicals.

Article Abstract

The Tibetan Plateau, known as the "Roof of the World" and "The Third Pole", harbors numerous saline lakes primarily distributed in the Northern Tibetan Plateau. However, the challenging conditions of high altitude, low oxygen level, and harsh climate have limited investigations into the actinobacteria from these saline lakes. This study focuses on investigating the biodiversity and bioactive secondary metabolites of cultivable actinobacteria isolated from the sediments of four saline lakes on the Northern Tibetan Plateau. A total of 255 actinobacterial strains affiliated with 21 genera in 12 families of 7 orders were recovered by using the pure culture technique and 16S rRNA gene phylogenetic analysis. To facilitate a high-throughput bioactivity evaluation, 192 isolates underwent OSMAC cultivation in a miniaturized 24-well microbioreactor system (MATRIX cultivation). The antibacterial activity of crude extracts was then evaluated in a 96-well plate antibacterial assay. Forty-six strains demonstrated antagonistic effects against at least one tested pathogen, and their underlying antibacterial mechanisms were further investigated through a dual-fluorescent reporter assay (pDualrep2). Two strains (378 and 549) that produce compounds triggering DNA damage were prioritized for subsequent chemical investigations. Metabolomics profiling involving HPLC-UV/vis, UPLC-QTOF-MS/MS, and molecular networking identified three types of bioactive metabolites belonging to the aromatic polyketide family, i.e., cosmomycin, kidamycin, and hedamycin. In-depth analysis of the metabolomic data unveiled some potentially novel anthracycline compounds. A genome mining study based on the whole-genome sequences of strains 378 and 549 identified gene clusters potentially responsible for cosmomycin and kidamycin biosynthesis. This work highlights the effectiveness of combining metabolomic and genomic approaches to rapidly identify bioactive chemicals within microbial extracts. The saline lakes on the Northern Tibetan Plateau present prospective sources for discovering novel actinobacteria and biologically active compounds.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609225PMC
http://dx.doi.org/10.3390/microorganisms11102475DOI Listing

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