scholarly journals Antitumor Anthraquinones from an Easter Island Sea Anemone: Animal or Bacterial Origin?

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 154 ◽  
Author(s):  
Ignacio Sottorff ◽  
Sven Künzel ◽  
Jutta Wiese ◽  
Matthias Lipfert ◽  
Nils Preußke ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Antitumor Activity ◽  
Genome Analysis ◽  
New Genus ◽  
Marine Invertebrate ◽  
Easter Island ◽  
Sea Anemone ◽  
Producer Strain ◽  
Marine Actinobacteria

The presence of two known anthraquinones, Lupinacidin A and Galvaquinone B, which have antitumor activity, has been identified in the sea anemone (Gyractis sesere) from Easter Island. So far, these anthraquinones have been characterized from terrestrial and marine Actinobacteria only. In order to identify the anthraquinones producer, we isolated Actinobacteria associated with the sea anemone and obtained representatives of seven actinobacterial genera. Studies of cultures of these bacteria by HPLC, NMR, and HRLCMS analyses showed that the producer of Lupinacidin A and Galvaquinone B indeed was one of the isolated Actinobacteria. The producer strain, SN26_14.1, was identified as a representative of the genus Verrucosispora. Genome analysis supported the biosynthetic potential to the production of these compounds by this strain. This study adds Verrucosispora as a new genus to the anthraquinone producers, in addition to well-known species of Streptomyces and Micromonospora. By a cultivation-based approach, the responsibility of symbionts of a marine invertebrate for the production of complex natural products found within the animal’s extracts could be demonstrated. This finding re-opens the debate about the producers of secondary metabolites in sea animals. Finally, it provides valuable information about the chemistry of bacteria harbored in the geographically-isolated and almost unstudied, Easter Island.

scholarly journals Phytoplankton trigger the production of cryptic metabolites in the marine actinobacteria Salinispora tropica

2020 ◽  
Author(s):  
Audam Chhun ◽  
Despoina Sousoni ◽  
Maria del Mar Aguiló-Ferretjans ◽  
Lijiang Song ◽  
Christophe Corre ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Antibiotic Production ◽  
Antimicrobial Effect ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Marine Actinobacteria ◽  
Salinispora Tropica ◽  
Eukaryotic Phytoplankton

AbstractBacteria from the Actinomycete family are a remarkable source of natural products with pharmaceutical potential. The discovery of novel molecules from these organisms is, however, hindered because most of the biosynthetic gene clusters (BGCs) encoding these secondary metabolites are cryptic or silent and are referred to as orphan BGCs. While co-culture has proven to be a promising approach to unlock the biosynthetic potential of many microorganisms by activating the expression of these orphan BGCs, it still remains an underexplored technique. The marine actinobacteria Salinispora tropica, for instance, produces valuable compounds such as the anti-cancer molecule salinosporamide A but half of its putative BGCs are still orphan. Although previous studies have looked into using marine heterotrophs to induce orphan BGCs in Salinispora, the potential impact of co-culturing marine phototrophs with Salinispora has yet to be investigated. Following the observation of clear antimicrobial phenotype of the actinobacterium on a range of phytoplanktonic organisms, we here report the discovery of novel cryptic secondary metabolites produced by S. tropica in response to its co-culture with photosynthetic primary producers. An approach combining metabolomics and proteomics revealed that the photosynthate released by phytoplankton influences the biosynthetic capacities of S. tropica with both production of new molecules and the activation of orphan BGCs. Our work pioneers the use of phototrophs as a promising strategy to accelerate the discovery of novel natural products from actinobacteria.ImportanceThe alarming increase of antimicrobial resistance has generated an enormous interest in the discovery of novel active compounds. The isolation of new microbes to untap novel natural products is currently hampered because most biosynthetic gene clusters (BGC) encoded by these microorganisms are not expressed under standard laboratory conditions, i.e. mono-cultures. Here we show that co-culturing can be an easy way for triggering silent BGC. By combining state-of-the-art metabolomics and high-throughput proteomics, we characterized the activation of cryptic metabolites and silent biosynthetic gene clusters in the marine actinobacteria Salinispora tropica by the presence of phytoplankton photosynthate. We further suggest a mechanistic understanding of the antimicrobial effect this actinobacterium has on a broad range of prokaryotic and eukaryotic phytoplankton species and reveal a promising candidate for antibiotic production.

Natural Products from Cyanobacteria with Antimicrobial and Antitumor Activity

2014 ◽  
Vol 14 (9) ◽  
pp. 820-828 ◽  
Author(s):  
Maria Silva-Stenico ◽  
Ramon Kaneno ◽  
Fabiana Zambuzi ◽  
Marcelo Vaz ◽  
Danillo Alvarenga ◽  
...  
Keyword(s):  
Natural Products ◽  
Antitumor Activity

Current Status on Natural Products with Antitumor Activity from Brazilian Marine Sponges

2012 ◽  
Vol 13 (1) ◽  
pp. 235-244 ◽  
Author(s):  
Mario Luiz Conte da Frota Junior ◽  
Renata Biegelmeyer da Silva ◽  
Beatriz Mothes ◽  
Amelia Teresinha Henriques ◽  
Jose Claudio Fonseca Moreira
Keyword(s):  
Natural Products ◽  
Antitumor Activity ◽  
Marine Sponges ◽  
Current Status

scholarly journals Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 107
Author(s):  
Rafael de Felício ◽  
Patricia Ballone ◽  
Cristina Freitas Bazzano ◽  
Luiz F. G. Alves ◽  
Renata Sigrist ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Deep Sea ◽  
Chemical Space ◽  
Bacterial Genome ◽  
Vast Number ◽  
Bacterial Metabolites ◽  
Laboratory Conditions ◽  
Deep Sea Bacteria

Bacterial genome sequencing has revealed a vast number of novel biosynthetic gene clusters (BGC) with potential to produce bioactive natural products. However, the biosynthesis of secondary metabolites by bacteria is often silenced under laboratory conditions, limiting the controlled expression of natural products. Here we describe an integrated methodology for the construction and screening of an elicited and pre-fractionated library of marine bacteria. In this pilot study, chemical elicitors were evaluated to mimic the natural environment and to induce the expression of cryptic BGCs in deep-sea bacteria. By integrating high-resolution untargeted metabolomics with cheminformatics analyses, it was possible to visualize, mine, identify and map the chemical and biological space of the elicited bacterial metabolites. The results show that elicited bacterial metabolites correspond to ~45% of the compounds produced under laboratory conditions. In addition, the elicited chemical space is novel (~70% of the elicited compounds) or concentrated in the chemical space of drugs. Fractionation of the crude extracts further evidenced minor compounds (~90% of the collection) and the detection of biological activity. This pilot work pinpoints strategies for constructing and evaluating chemically diverse bacterial natural product libraries towards the identification of novel bacterial metabolites in natural product-based drug discovery pipelines.

scholarly journals Crocus sativus L. Extract and Its Constituents: Chemistry, Pharmacology and Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4226
Author(s):  
Nikolaos Pitsikas ◽  
Konstantinos Dimas
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Organic Compounds ◽  
Therapeutic Potential ◽  
Crocus Sativus ◽  
Natural Sources ◽  
Crocus Sativus L

Natural products or organic compounds isolated from natural sources as primary or secondary metabolites have inspired numerous drugs [...]

scholarly journals MeFSAT: a curated natural product database specific to secondary metabolites of medicinal fungi

RSC Advances ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 2596-2607
Author(s):  
R. P. Vivek-Ananth ◽  
Ajaya Kumar Sahoo ◽  
Kavyaa Kumaravel ◽  
Karthikeyan Mohanraj ◽  
Areejit Samal
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Chemical Space ◽  
Therapeutic Uses ◽  
Medicinal Fungi ◽  
Fungal Natural Products

First dedicated manually curated resource on secondary metabolites and therapeutic uses of medicinal fungi. Cheminformatics based analysis of the chemical space of fungal natural products.

scholarly journals Natural Products in Polyclad Flatworms

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 47
Author(s):  
Justin M. McNab ◽  
Jorge Rodríguez ◽  
Peter Karuso ◽  
Jane E. Williamson
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Marine Invertebrates ◽  
Symbiotic Bacteria ◽  
Chemical Defences ◽  
Number Of Species ◽  
Bioactive Secondary Metabolites ◽  
Potential Sources ◽  
Polyclad Flatworms

Marine invertebrates are promising sources of novel bioactive secondary metabolites, and organisms like sponges, ascidians and nudibranchs are characterised by possessing potent defensive chemicals. Animals that possess chemical defences often advertise this fact with aposematic colouration that potential predators learn to avoid. One seemingly defenceless group that can present bright colouration patterns are flatworms of the order Polycladida. Although members of this group have typically been overlooked due to their solitary and benthic nature, recent studies have isolated the neurotoxin tetrodotoxin from these mesopredators. This review considers the potential of polyclads as potential sources of natural products and reviews what is known of the activity of the molecules found in these animals. Considering the ecology and diversity of polyclads, only a small number of species from both suborders of Polycladida, Acotylea and Cotylea have been investigated for natural products. As such, confirming assumptions as to which species are in any sense toxic or if the compounds they use are biosynthesised, accumulated from food or the product of symbiotic bacteria is difficult. However, further research into the group is suggested as these animals often display aposematic colouration and are known to prey on invertebrates rich in bioactive secondary metabolites.

scholarly journals Computer-Aided Drug Design (CADD) to De-Orphanize Marine Molecules: Finding Potential Therapeutic Agents for Neurodegenerative and Cardiovascular Diseases

Marine Drugs ◽  
2022 ◽  
Vol 20 (1) ◽  
pp. 53
Author(s):  
Laura Llorach-Pares ◽  
Alfons Nonell-Canals ◽  
Conxita Avila ◽  
Melchor Sanchez-Martinez
Keyword(s):  
Natural Products ◽  
Drug Design ◽  
Therapeutic Potential ◽  
Marine Invertebrate ◽  
In Silico Analysis ◽  
New Drugs ◽  
Computer Aided Drug Design ◽  
Marine Habitats ◽  
Computer Aided ◽  
Promising Line

Computer-aided drug design (CADD) techniques allow the identification of compounds capable of modulating protein functions in pathogenesis-related pathways, which is a promising line on drug discovery. Marine natural products (MNPs) are considered a rich source of bioactive compounds, as the oceans are home to much of the planet’s biodiversity. Biodiversity is directly related to chemodiversity, which can inspire new drug discoveries. Therefore, natural products (NPs) in general, and MNPs in particular, have been used for decades as a source of inspiration for the design of new drugs. However, NPs present both opportunities and challenges. These difficulties can be technical, such as the need to dive or trawl to collect the organisms possessing the compounds, or biological, due to their particular marine habitats and the fact that they can be uncultivable in the laboratory. For all these difficulties, the contributions of CADD can play a very relevant role in simplifying their study, since, for example, no biological sample is needed to carry out an in-silico analysis. Therefore, the amount of natural product that needs to be used in the entire preclinical and clinical study is significantly reduced. Here, we exemplify how this combination between CADD and MNPs can help unlock their therapeutic potential. In this study, using a set of marine invertebrate molecules, we elucidate their possible molecular targets and associated therapeutic potential, establishing a pipeline that can be replicated in future studies.

scholarly journals SECONDARY METABOLITES WITH ANTIBIOTIC ACTIVITY OF MARINE ACTINOBACTERIA

2021 ◽  
pp. 28-43
Author(s):  
K. S. Potapenko ◽  
N. V. Korotaieva ◽  
V. О. Ivanytsia
Keyword(s):  
Secondary Metabolites ◽  
Plant Growth ◽  
Bioactive Compounds ◽  
Current Literature ◽  
Antibiotic Activity ◽  
Growth Hormones ◽  
Biologically Active ◽  
Marine Actinobacteria ◽  
Biotechnological Potential ◽  
Plant Growth Hormones

Marine actinobacteria are active producers and an unused rich source of various biologically active secondary metabolites, such as antibiotics, antitumor, antiviral and antiinflammatory compounds, biopesticides, plant growth hormones, pigments, enzymes, enzyme inhibitors.In this review describes data from current literature sources for the period from 2017 to 2021 about various bioactive compounds that produce marine actinobacteria, their antibiotic activity and biotechnological potential, the main groups of secondary metabolites and their producers.

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