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Bioactive Secondary Metabolites from Octocoral-Associated Microbes-New Chances for Blue Growth.

ABSTRACT: Octocorals (Cnidaria, Anthozoa Octocorallia) are magnificent repositories of natural products with fascinating and unusual chemical structures and bioactivities of interest to medicine and biotechnology. However, mechanistic understanding of the contribution of microbial symbionts to the chemical diversity of octocorals is yet to be achieved. This review inventories the natural products so-far described for octocoral-derived bacteria and fungi, uncovering a true chemical arsenal of terpenes, steroids, alkaloids, and polyketides with antibacterial, antifungal, antiviral, antifouling, anticancer, anti-inflammatory, and antimalarial activities of enormous potential for blue growth. Genome mining of 15 bacterial associates (spanning 12 genera) cultivated from Eunicella spp. resulted in the identification of 440 putative and classifiable secondary metabolite biosynthetic gene clusters (BGCs), encompassing varied terpene-, polyketide-, bacteriocin-, and nonribosomal peptide-synthase BGCs. This points towards a widespread yet uncharted capacity of octocoral-associated bacteria to synthetize a broad range of natural products. However, to extend our knowledge and foster the near-future laboratory production of bioactive compounds from (cultivatable and currently uncultivatable) octocoral symbionts, optimal blending between targeted metagenomics, DNA recombinant technologies, improved symbiont cultivation, functional genomics, and analytical chemistry are required. Such a multidisciplinary undertaking is key to achieving a sustainable response to the urgent industrial demand for novel drugs and enzyme varieties.

SUBMITTER: Raimundo I

PROVIDER: S-EPMC6316421 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Project description:Microbial secondary metabolites play crucial roles in microbial competition, communication, resource acquisition, antibiotic production, and a variety of other biotechnological processes. The retrieval of full-length BGC (biosynthetic gene cluster) sequences from uncultivated bacteria is difficult due to the technical constraints of short-read sequencing, making it impossible to determine BGC diversity. Using long-read sequencing and genome mining, 339 mainly full-length BGCs were recovered in this study, illuminating the wide range of BGCs from uncultivated lineages discovered in seawater from Aoshan Bay, Yellow Sea, China. Many extremely diverse BGCs were discovered in bacterial phyla such as Proteobacteria, Bacteroidota, Acidobacteriota, and Verrucomicrobiota as well as the previously uncultured archaeal phylum "Candidatus Thermoplasmatota." The data from metatranscriptomics showed that 30.1% of secondary metabolic genes were being expressed, and they also revealed the expression pattern of BGC core biosynthetic genes and tailoring enzymes. Taken together, our results demonstrate that long-read metagenomic sequencing combined with metatranscriptomic analysis provides a direct view into the functional expression of BGCs in environmental processes. IMPORTANCE Genome mining of metagenomic data has become the preferred method for the bioprospecting of novel compounds by cataloguing secondary metabolite potential. However, the accurate detection of BGCs requires unfragmented genomic assemblies, which have been technically difficult to obtain from metagenomes until recently with new long-read technologies. We used high-quality metagenome-assembled genomes generated from long-read data to determine the biosynthetic potential of microbes found in the surface water of the Yellow Sea. We recovered 339 highly diverse and mostly full-length BGCs from largely uncultured and underexplored bacterial and archaeal phyla. Additionally, we present long-read metagenomic sequencing combined with metatranscriptomic analysis as a potential method for gaining access to the largely underutilized genetic reservoir of specialized metabolite gene clusters in the majority of microbes that are not cultured. The combination of long-read metagenomic and metatranscriptomic analyses is significant because it can more accurately assess the mechanisms of microbial adaptation to the environment through BGC expression based on metatranscriptomic data.

Project description:Lichens are symbiotic organisms composed of at least one fungal and one algal species. They are found in different environments around the world, even in the poles and deserts. Some species can withstand extreme abiotic conditions, including radiation and the vacuum of space. Their chemistry is mainly due to the fungal metabolism and the production of several secondary metabolites with biological activity, which have been isolated due to an increasing interest from the pharmaceutical community. However, beyond the experimental data, little is known about their mechanisms of action and the potential pharmaceutical use of these kinds of molecules, especially the ones isolated from lesser-known species and/or lesser-studied countries. The main objective of this review is to analyze the bibliographical data of the biological activity of secondary metabolites from lichens, identifying the possible mechanisms of action and lichen species from Chile. We carried out a bibliographic revision of different scientific articles in order to collect all necessary information on the biological activity of the metabolites of these lichen species. For this, validated databases were used. We found the most recent reports where in vitro and in vivo studies have demonstrated the biological properties of these metabolites. The biological activity, namely anticancer, antioxidant, and anti-inflammatory activity, of 26 secondary metabolites are described, as well as their reported molecular mechanisms. The most notable metabolites found in this review were usnic acid, atranorin, protolichesterinic acid, and lobaric acid. Usnic acid was the most investigated metabolite, in addition to undergoing toxicological and pharmacological studies, where a hepatotoxicity effect was reported due to uncoupling oxidative phosphorylation. Additionally, no major studies have been made to validate the pharmacological application of these metabolites, and few advancements have been made in their artificial growth in bioreactors. Despite the described biological activities, there is little support to consider these metabolites in pharmaceutical formulations or to evaluate them in clinical trials. Nevertheless, it is important to carry out further studies regarding their possible human health effects. These lichen secondary metabolites present a promising research opportunity to find new pharmaceutical molecules due to their bioactive properties.

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Bioactive Secondary Metabolites from Octocoral-Associated Microbes-New Chances for Blue Growth.

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