Discovery of a New Asymmetric Dimer Nenestatin B and Implications of Dimerizing Enzyme in a Deep Sea Actinomycete

2021 ◽  
Author(s):  
Xiaodong Jiang ◽  
Zhuangjie Fang ◽  
Qingbo Zhang ◽  
Wei Liu ◽  
Liping Zhang ◽  
...  
Keyword(s):  
Natural Products ◽  
Broad Spectrum ◽  
Deep Sea ◽  
Important Family ◽  
Asymmetric Dimer

Benzofluorene-containing atypical angucyclines are an important family of natural products with a broad spectrum of antibacterial and cytotoxic properties. Interestingly, symmetric and asymmetric dimer showed better activity than the monomer...

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 Deep-sea natural products

2008 ◽  
Vol 25 (6) ◽  
pp. 1131 ◽  
Author(s):  
Danielle Skropeta
Keyword(s):  
Natural Products ◽  
Deep Sea

Deep-Sea Hydrothermal Vents: Potential Hot Spots for Natural Products Discovery?⊥

2010 ◽  
Vol 73 (3) ◽  
pp. 489-499 ◽  
Author(s):  
Christopher C. Thornburg ◽  
T. Mark Zabriskie ◽  
Kerry L. McPhail
Keyword(s):  
Natural Products ◽  
Deep Sea ◽  
Hot Spots ◽  
Hydrothermal Vents ◽  
Natural Products Discovery

scholarly journals Discovery of Allopregnanolone Against Influenza Virus With Broad Spectrum in Vitro

2021 ◽  
Author(s):  
yuqi Wang ◽  
Yanyan Wang ◽  
Hong Cao
Keyword(s):  
Natural Products ◽  
Influenza Virus ◽  
Viral Replication ◽  
Broad Spectrum ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Wild Type Virus ◽  
Dependent Manner ◽  
Viral Yield

Abstract Background: Influenza virus infection with seasonal or occasional but devastating morbidity and mortality, is a severe threat to public health. The frequent emergence of resistant viral strains limited application of current antivirals and posing an urgent need for novel antiviral therapies. Natural products offered a broad prospect in the screening and development of new influenza inhibitors.Methods: In this research, a high-throughput antiviral screening for 891 natural products was performed based on a recombinant reporter influenza A virus. According to the cytotoxicity assay and dose-response relationship, alloprogesterone (ALLO), as the positive hit was selected, and verified by viral titer reduction assay and immunofluorescence using a wild-type virus. Followingly, we explored its antiviral potency of counteracting with IAV and IBV, and preliminary investigated the mechanism of ALLO through time-of-addition assay and mini-replicon system.Results: Under the criteria of 80% inhibition and 70% cell viability, ALLO was screened out and confirmed antiviral activity in varied cells. The inhibitory effect of ALLO against influenza virus with a dose-dependent manner and significantly reduced viral yield of five different influenza viruses in the presence of 40 µM ALLO, including oseltamivir-resistant virus. Moreover, ALLO exhibited no influence on IAV entry or release during the viral replication cycle, but obviously interfered with the genome replication regarding post-infection 2 hrs to 6 hrs, which is consistent with the evidence of decreased polymerase activity.Conclusions: In summary, we firstly identified a new pharmacological activity of ALLO, as a broad spectrum inhibitor for treatment influenza infections, targeting viral replication stage and possessing great value of further development.

scholarly journals Targeting tRNA-Synthetase Interactions towards Novel Therapeutic Discovery Against Eukaryotic Pathogens

2019 ◽  
Author(s):  
Paul Kelly ◽  
Fatemeh Hadi-Nezhad ◽  
Dennis Liu ◽  
Travis J. Lawrence ◽  
Roger G. Linington ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Broad Spectrum ◽  
Marine Natural Products ◽  
Drug Targets ◽  
Leishmania Major ◽  
Trna Synthetase ◽  
Cross Reactivity ◽  
Protein Synthesis Inhibitors ◽  
Macromolecular Interactions

AbstractThe development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and eight clades of trypanosomes, identifying parasite-specific informative features (including base-pairs and base mis-pairs) that are broadly conserved over approximately 250 million years of trypanosome evolution. Validating these observations, we demonstrated biochemically that tRNA:aminoacyl-tRNA synthetase interactions are a promising target for anti-trypanosomal drug discovery. From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. These findings support a systems biology model in which combination chemotherapies that target multiple tRNA-synthetase interactions should be comparatively less prone to the emergence of resistance than conventional single drug therapies.Author SummaryTrypanosome parasites pose a significant health risk worldwide. Conventional drug development strategies have proven challenging given the high conservation between humans and pathogens, with off-target toxicity being a common problem. Protein synthesis inhibitors have historically been an attractive target for antimicrobial discovery against bacteria, and more recently for eukaryotic pathogens. Here we propose that exploiting pathogen-specific tRNA-synthetase interactions offers the potential for highly targeted drug discovery. To this end, we improved tRNA gene annotations in trypanosome genomes, identified functionally informative trypanosome-specific tRNA features, and showed that these features are highly conserved over approximately 250 million years of trypanosome evolution. Highlighting the species-specific and broad-spectrum potential of our approach, we identified natural product inhibitors against the parasite translational machinery that have no effect on the homologous human enzyme.

scholarly journals Strategies To Access γ-Hydroxy-γ-butyrolactams

Synthesis ◽  
2018 ◽  
Vol 50 (06) ◽  
pp. 1175-1198 ◽  
Author(s):  
Laurent Commeiras ◽  
Muhammad Idham Darussalam Mardjan ◽  
Jean-Luc Parrain
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Broad Spectrum ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Building Blocks ◽  
Pharmaceutical Molecules

α,β-Unsaturated γ-hydroxy-γ-butyrolactams are of a great interest due to their presence in designed pharmaceutical molecules and numerous natural products displaying a broad spectrum of biological activities. In addition, these five-membered heterocyclic compounds are also relevant and versatile building blocks in organic synthesis. In this context, strategies for the construction of these scaffolds has triggered considerable attention and this review highlights the progress in the formation of α,β-unsaturated γ-hydroxy-γ-butyrolactams (5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones).1 Introduction2 Intramolecular Routes3 Intermolecular Routes4 Oxidation of Heterocyclic Compounds5 Miscellaneous6 Conclusion

Natural Products from Deep-Sea-Derived Fungi ̶ A New Source of Novel Bioactive Compounds?

2018 ◽  
Vol 25 (2) ◽  
pp. 186-207 ◽  
Author(s):  
Georgios Daletos ◽  
Weaam Ebrahim ◽  
Elena Ancheeva ◽  
Mona El-Neketi ◽  
Weiguo Song ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Secondary Metabolites ◽  
Bioactive Compounds ◽  
Deep Sea ◽  
Underlying Assumption ◽  
Pharmacologically Active ◽  
Promising Source ◽  
New Metabolites

Background: Over the last two decades, deep-sea-derived fungi are considered to be a new source of pharmacologically active secondary metabolites for drug discovery mainly based on the underlying assumption that the uniqueness of the deep sea will give rise to equally unprecedented natural products. Indeed, up to now over 200 new metabolites have been identified from deep-sea fungi, which is in support of the statement made above. Results: This review summarizes the new and/or bioactive compounds reported from deepsea- derived fungi in the last six years (2010 – October 2016) and critically evaluates whether the data published so far really support the notion that these fungi are a promising source of new bioactive chemical entities.

scholarly journals The Bristol Sponge Microbiome Collection: A Unique Repository of Deep-Sea Microorganisms and Associated Natural Products

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 509
Author(s):  
Sam E. Williams ◽  
Henry L. Stennett ◽  
Catherine R. Back ◽  
Kavita Tiwari ◽  
Jorge Ojeda Gomez ◽  
...  
Keyword(s):  
Natural Products ◽  
Deep Sea ◽  
Molecular Genetic ◽  
Deep Ocean ◽  
Marine Sponges ◽  
Environmental Niche ◽  
Lead Compounds ◽  
Using Data ◽  
Life On Earth ◽  
Analytical Tools

The deep ocean is the largest habitat for life on Earth, though the microorganisms that occupy this unique environmental niche remain largely unexplored. Due to the significant logistical and operational challenges associated with accessing the deep ocean, bioprospecting programmes that seek to generate novel products from marine organisms have, to date, focused predominantly on samples recovered from shallow seas. For this reason, the deep ocean remains a largely untapped resource of novel microbiological life and associated natural products. Here we report the establishment of the Bristol Sponge Microbiome Collection (BISECT), a unique repository of deep-sea microorganisms and associated metabolites isolated from the microbiota of marine sponges, recovered from previously unsurveyed regions of the mid Atlantic Ocean, at depths of 0.3–3 km. An integrated biodiscovery pipeline comprising molecular, genetic, bioinformatic and analytical tools is also described, which is being applied to interrogate this collection. The potential of this approach is illustrated using data reporting our initial efforts to identify antimicrobial natural product lead compounds. Prospects for the use of BISECT to address allied pharmaceutical needs, along with mechanisms of access to the collection are also discussed

scholarly journals A New Micromonospora Strain with Antibiotic Activity Isolated from the Microbiome of a Mid-Atlantic Deep-Sea Sponge

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 105
Author(s):  
Catherine R. Back ◽  
Henry L. Stennett ◽  
Sam E. Williams ◽  
Luoyi Wang ◽  
Jorge Ojeda Gomez ◽  
...  
Keyword(s):  
Natural Products ◽  
Deep Sea ◽  
Bacterial Communities ◽  
Resource Competition ◽  
Multidrug Resistant ◽  
Antibiotic Activity ◽  
Bioactive Metabolites ◽  
Microbial Life ◽  
Potential Source ◽  
Fermentation Broths

To tackle the growing problem of antibiotic resistance, it is essential to identify new bioactive compounds that are effective against resistant microbes and safe to use. Natural products and their derivatives are, and will continue to be, an important source of these molecules. Sea sponges harbour a diverse microbiome that co-exists with the sponge, and these bacterial communities produce a rich array of bioactive metabolites for protection and resource competition. For these reasons, the sponge microbiota constitutes a potential source of clinically relevant natural products. To date, efforts in bioprospecting for these compounds have focused predominantly on sponge specimens isolated from shallow water, with much still to be learned about samples from the deep sea. Here we report the isolation of a new Micromonospora strain, designated 28ISP2-46T, recovered from the microbiome of a mid-Atlantic deep-sea sponge. Whole-genome sequencing reveals the capacity of this bacterium to produce a diverse array of natural products, including kosinostatin and isoquinocycline B, which exhibit both antibiotic and antitumour properties. Both compounds were isolated from 28ISP2-46T fermentation broths and were found to be effective against a plethora of multidrug-resistant clinical isolates. This study suggests that the marine production of isoquinocyclines may be more widespread than previously supposed and demonstrates the value of targeting the deep-sea sponge microbiome as a source of novel microbial life with exploitable biosynthetic potential.

scholarly journals Antimicrobial activity of selected natural products against Gram-positive, Gram-negative and Acid-fast bacterial pathogens

2012 ◽  
Vol 2 (1) ◽  
pp. 13 ◽  
Author(s):  
Niket Yadav ◽  
Ekta Yadav ◽  
Jagjit S. Yadav
Keyword(s):  
Natural Products ◽  
Broad Spectrum ◽  
Curcuma Longa ◽  
Bacterial Species ◽  
Zingiber Officinale ◽  
Variable Order ◽  
Root Extract ◽  
Gram Positive ◽  
Gram Negative ◽  
Eucalyptus Oil

Recurring epidemics of drug resistant bacterial diseases such as those caused by mycobacteria (tuberculosis and non-tuberculous infections), staphylococci (methicillin-resistant <em>Staphylococcus aureus</em> or MRSA infections) and various Gram-negative enterobacteria (enterobacterial infections) have reinforced the need to search for alternative antimicrobials. In this context, we investigated the anti-bacterial potential of nine different natural products and compared them with the antibiotic controls, using three test bacterial species, representing the Gram-negative (<em>Escherichia coli</em>), Gram-positive (<em>Staphylococcus epidermidis</em>), and Acid-fast (<em>Mycobacterium smegmatis</em>) pathogen groups. Six of the nine products showed detectable but variable zones of inhibition (mm2). The anti-bacterial activity (mm2 per 100 mg) of the extracts from the four solid natural products was in the following order for all three pathogen groups: Mint (<em>Mentha arvensis</em>) leaf extract, 264-930&gt;Mushroom (<em>Agaricus bisporus</em>) cap extract, 112-241&gt;Turmeric (<em>Curcuma longa</em>) root extract, 4-10&gt;Ginger (<em>Zingiber officinale</em>) root extract, 3-9. For the liquid products, the activity measured on 100 μL aliquots was in the following order: Eucalyptus (<em>Eucalyptus globules</em>) oil, 264-1044&gt;Mustard (<em>Brassica campestris</em> L. var. brown sarson) oil, 45-96. Taken together, these results indicated the highest activity in Mint extract and Eucalyptus oil against all three test organisms. However, the individual test strains showed the following variable order of susceptibility: Mint extract (<em>M. smegmatis</em>&gt;<em>E. coli</em>&gt;<em>S</em>. <em>epidermidis</em>); Eucalyptus oil (<em>M. smegmatis</em>&gt;<em>S. epidermidis</em>&gt;<em>E</em>. <em>coli</em>). Based on these results it can be concluded that Mint leaves and Eucalyptus oil have an unusually broad spectrum activity and may, therefore, be promising sources of new broad spectrum antimicrobials.

Sign in / Sign up

Export Citation Format

Share Document