Planctomycetes are conspicuous, ubiquitous, environmentally important bacteria. They can attach to various surfaces in aquatic habitats and form biofilms. Their unique FtsZ-independent budding cell division mechanism is associated with slow growth and doubling times from 6 h up to 1 month. Despite this putative disadvantage in the struggle to colonize surfaces, Planctomycetes are frequently associated with aquatic phototrophic organisms such as diatoms, cyanobacteria or kelp, whereby Planctomycetes can account for up to 50% of the biofilm-forming bacterial population. Consequently, Planctomycetes were postulated to play an important role in carbon utilization, for example as scavengers after phototrophic blooms. However, given their observed slow growth, such findings are surprising since other faster- growing heterotrophs tend to colonize similar ecological niches. Accordingly, Planctomycetes were suspected to produce antibiotics for habitat protection in response to the attachment on phototrophs. Recently, we demonstrated their genomic potential to produce non-ribosomal peptides, polyketides, bacteriocins, and terpenoids that might have antibiotic activities. In this study, we describe the development of a pipeline that consists of tools and procedures to cultivate Planctomycetes for the production of antimicrobial compounds in a chemically defined medium and a procedure to chemically mimic their interaction with other organisms such as for example cyanobacteria. We evaluated and adjusted screening assays to enable the hunt for planctomycetal antibiotics. As proof of principle, we demonstrate antimicrobial activities of planctomycetal extracts from Planctopirus limnophila DSM 3776, Rhodopirellula baltica DSM 10527, and the recently isolated strain Pan216. By combining UV/Vis and high resolution mass spectrometry data from high-performance liquid chromatography fractionations with growth inhibition of indicator strains, we were able to assign the antibiotic activity to candidate peaks related to planctomycetal antimicrobial compounds. The MS analysis points toward the production of novel bioactive molecules with novel structures. Consequently, we developed a large scale cultivation procedure to allow future structural elucidation of such compounds. Our findings might have implications for the discovery of novel antibiotics as Planctomycetes represent a yet untapped resource that could be developed by employing the tools and methods described in this study.
A 3-decalinoyltetramic acid, for which the trivial name hymenosetin is proposed, was isolated from crude extracts of a virulent strain of the ash dieback pathogen, Hymenoscyphus pseudoalbidus (= "Chalara fraxinea"). This compound was produced only under certain culture conditions in submerged cultures of the fungus. Its planar structure was determined by NMR spectroscopy and by mass spectrometry. The absolute stereochemistry was assigned by CD spectroscopy and HETLOC data. Hymenosetin exhibited broad spectrum antibacterial and antifungal activities (including strong inhibition of MRSA, as well as moderate cytotoxic effects.So far, the metabolite proved inactive in assays for evaluation of phytotoxicity, whereas viridiol, another secondary metabolite known from H. pseudoalbidus, was regarded as phytotoxic principle of the pathogen against its host, Fraxinus excelsior. Further studies will show whether hymenosetin constitutes a defence metabolite that is produced by the pathogenic fungus to combat other microbes and fungi in the natural environment.
Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.
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