scholarly journals Bioactivity Screening and Gene-Trait Matching across Marine Sponge-Associated Bacteria

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 75
Author(s):  
Asimenia Gavriilidou ◽  
Thomas Andrew Mackenzie ◽  
Pilar Sánchez ◽  
José Ruben Tormo ◽  
Colin Ingham ◽  
...  
Keyword(s):  
Natural Products ◽  
Gene Clusters ◽  
Marine Sponges ◽  
Genetic Associations ◽  
Bioactive Substances ◽  
Associated Bacteria ◽  
Peptide Synthetases ◽  
Sponge Associated Bacteria ◽  
High Cytotoxicity

Marine sponges harbor diverse microbial communities that represent a significant source of natural products. In the present study, extracts of 21 sponge-associated bacteria were screened for their antimicrobial and anticancer activity, and their genomes were mined for secondary metabolite biosynthetic gene clusters (BGCs). Phylogenetic analysis assigned the strains to four major phyla in the sponge microbiome, namely Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes. Bioassays identified one extract with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity, and more than 70% of the total extracts had a moderate to high cytotoxicity. The most active extracts were derived from the Proteobacteria and Actinobacteria, prominent for producing bioactive substances. The strong bioactivity potential of the aforementioned strains was also evident in the abundance of BGCs, which encoded mainly beta-lactones, bacteriocins, non-ribosomal peptide synthetases (NRPS), terpenes, and siderophores. Gene-trait matching was performed for the most active strains, aiming at linking their biosynthetic potential with the experimental results. Genetic associations were established for the anti-MRSA and cytotoxic phenotypes based on the similarity of the detected BGCs with BGCs encoding natural products with known bioactivity. Overall, our study highlights the significance of combining in vitro and in silico approaches in the search of novel natural products of pharmaceutical interest.

Biotechnological Potential of Marine Sponges and their Associated Bacteria as Producers of New Pharmaceuticals (Part I)

2005 ◽  
Vol 2 (5) ◽  
Author(s):  
Carsten Thoms ◽  
Peter Schupp
Keyword(s):  
Natural Products ◽  
Large Scale ◽  
Marine Sponges ◽  
Sponge Tissue ◽  
Associated Bacteria ◽  
Biotechnological Potential ◽  
Highly Active ◽  
Medicinal Treatment ◽  
Microbial Infections ◽  
Sponge Associated Bacteria

AbstractThroughout human history natural products have provided the basis for medicinal treatment. About 60 years ago the advent of SCUBA diving techniques granted access to a thitherto untapped source of pharmacologically highly active natural products: the marine environment. In the oceans not plants but sessile animals, particularly sponges, have proven to be the most fruitful organisms in this context. Sponges have evolved a vast arsenal of chemical weapons to defend themselves against various threats from their environment. These molecules remarkably often show potent activities in pharmaceutical assays. Several sponge-derived compounds are already in clinical trials as agents against cancer, microbial infections, inflammation and other diseases. However, in many cases drug development is severely hampered by the limited supply of the respective compounds, as they are often present only in minute amounts in the sponge tissue. Big hope to circumvent this obstacle lies on the supposition that sponge-associated bacteria and not the sponges themselves are in many cases the true producers of the pharmaceutically relevant agents. Once these microorganisms are determined and cultivated outside the sponge tissue, they could be fermented for large-scale compound production. This in future could substantially increase the number of powerful sponge-derived drugs on the market.

scholarly journals Genome Reduction and Secondary Metabolism of the Marine Sponge-Associated Cyanobacterium Leptothoe

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 298
Author(s):  
Despoina Konstantinou ◽  
Rafael V. Popin ◽  
David P. Fewer ◽  
Kaarina Sivonen ◽  
Spyros Gkelis
Keyword(s):  
Natural Products ◽  
Microbial Communities ◽  
Genomic Analysis ◽  
Gene Clusters ◽  
Marine Sponges ◽  
Genome Reduction ◽  
Extracellular Polysaccharides ◽  
Comparative Genomic ◽  
Symbiotic Relationships ◽  
Genes Encoding

Sponges form symbiotic relationships with diverse and abundant microbial communities. Cyanobacteria are among the most important members of the microbial communities that are associated with sponges. Here, we performed a genus-wide comparative genomic analysis of the newly described marine benthic cyanobacterial genus Leptothoe (Synechococcales). We obtained draft genomes from Le. kymatousa TAU-MAC 1615 and Le. spongobia TAU-MAC 1115, isolated from marine sponges. We identified five additional Leptothoe genomes, host-associated or free-living, using a phylogenomic approach, and the comparison of all genomes showed that the sponge-associated strains display features of a symbiotic lifestyle. Le. kymatousa and Le. spongobia have undergone genome reduction; they harbored considerably fewer genes encoding for (i) cofactors, vitamins, prosthetic groups, pigments, proteins, and amino acid biosynthesis; (ii) DNA repair; (iii) antioxidant enzymes; and (iv) biosynthesis of capsular and extracellular polysaccharides. They have also lost several genes related to chemotaxis and motility. Eukaryotic-like proteins, such as ankyrin repeats, playing important roles in sponge-symbiont interactions, were identified in sponge-associated Leptothoe genomes. The sponge-associated Leptothoe stains harbored biosynthetic gene clusters encoding novel natural products despite genome reduction. Comparisons of the biosynthetic capacities of Leptothoe with chemically rich cyanobacteria revealed that Leptothoe is another promising marine cyanobacterium for the biosynthesis of novel natural products.

scholarly journals Multi-Omic Profiling of Melophlus Sponges Reveals Diverse Metabolomic and Microbiome Architectures that Are Non-overlapping with Ecological Neighbors

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 124 ◽  
Author(s):  
Ipsita Mohanty ◽  
Sheila Podell ◽  
Jason S. Biggs ◽  
Neha Garg ◽  
Eric E. Allen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Candidate Gene ◽  
Marine Sponge ◽  
Gene Clusters ◽  
Marine Sponges ◽  
Quantitative Comparison ◽  
Filter Feeding ◽  
Chemical Structures ◽  
Ecological Relevance

Marine sponge holobionts, defined as filter-feeding sponge hosts together with their associated microbiomes, are prolific sources of natural products. The inventory of natural products that have been isolated from marine sponges is extensive. Here, using untargeted mass spectrometry, we demonstrate that sponges harbor a far greater diversity of low-abundance natural products that have evaded discovery. While these low-abundance natural products may not be feasible to isolate, insights into their chemical structures can be gleaned by careful curation of mass fragmentation spectra. Sponges are also some of the most complex, multi-organismal holobiont communities in the oceans. We overlay sponge metabolomes with their microbiome structures and detailed metagenomic characterization to discover candidate gene clusters that encode production of sponge-derived natural products. The multi-omic profiling strategy for sponges that we describe here enables quantitative comparison of sponge metabolomes and microbiomes to address, among other questions, the ecological relevance of sponge natural products and for the phylochemical assignment of previously undescribed sponge identities.

scholarly journals An Orphan MbtH-Like Protein Interacts with Multiple Nonribosomal Peptide Synthetases inMyxococcus xanthusDK1622

2018 ◽  
Vol 200 (21) ◽  
Author(s):  
Karla J. Esquilín-Lebrón ◽  
Tye O. Boynton ◽  
Lawrence J. Shimkets ◽  
Michael G. Thomas
Keyword(s):  
Myxococcus Xanthus ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Nonribosomal Peptide ◽  
Content Type ◽  
Nonribosomal Peptide Synthetases ◽  
Peptide Synthetases

ABSTRACTOne mechanism by which bacteria and fungi produce bioactive natural products is the use of nonribosomal peptide synthetases (NRPSs). Many NRPSs in bacteria require members of the MbtH-like protein (MLP) superfamily for their solubility or function. Although MLPs are known to interact with the adenylation domains of NRPSs, the role MLPs play in NRPS enzymology has yet to be elucidated. MLPs are nearly always encoded within the biosynthetic gene clusters (BGCs) that also code for the NRPSs that interact with the MLP. Here, we identify 50 orphan MLPs from diverse bacteria. An orphan MLP is one that is encoded by a gene that is not directly adjacent to genes predicted to be involved in nonribosomal peptide biosynthesis. We targeted the orphan MLP MXAN_3118 fromMyxococcus xanthusDK1622 for characterization. TheM. xanthusDK1622 genome contains 15 NRPS-encoding BGCs but only one MLP-encoding gene (MXAN_3118). We tested the hypothesis that MXAN_3118 interacts with one or more NRPS using a combination ofin vivoandin vitroassays. We determined that MXAN_3118 interacts with at least seven NRPSs from distinct BGCs. We show that one of these BGCs codes for NRPS enzymology that likely produces a valine-rich natural product that inhibits the clumping ofM. xanthusDK1622 in liquid culture. MXAN_3118 is the first MLP to be identified that naturally interacts with multiple NRPS systems in a single organism. The finding of an MLP that naturally interacts with multiple NRPS systems suggests it may be harnessed as a “universal” MLP for generating functional hybrid NRPSs.IMPORTANCEMbtH-like proteins (MLPs) are essential accessory proteins for the function of many nonribosomal peptide synthetases (NRPSs). We identified 50 MLPs from diverse bacteria that are coded by genes that are not located near any NRPS-encoding biosynthetic gene clusters (BGCs). We define these as orphan MLPs because their NRPS partner(s) is unknown. Investigations into the orphan MLP fromMyxococcus xanthusDK1622 determined that it interacts with NRPSs from at least seven distinct BGCs. Support for these MLP-NRPS interactions came from the use of a bacterial two-hybrid assay and copurification of the MLP with various NRPSs. The flexibility of this MLP to naturally interact with multiple NRPSs led us to hypothesize that this MLP may be used as a “universal” MLP during the construction of functional hybrid NRPSs.

scholarly journals Expansion of gamma-butyrolactone signaling molecule biosynthesis to phosphotriester natural products

2020 ◽  
Author(s):  
Yuta Kudo ◽  
Takayoshi Awakawa ◽  
Yi-Ling Du ◽  
Peter A. Jordan ◽  
Kaitlin E. Creamer ◽  
...  
Keyword(s):  
Natural Products ◽  
Gene Clusters ◽  
Biosynthetic Gene Clusters ◽  
Physiological Processes ◽  
Marine Actinomycete ◽  
Structural Differences ◽  
Species Specific ◽  
Gamma Butyrolactone

AbstractBacterial hormones, such as the iconic gamma-butyrolactone A-factor, are essential signaling molecules that regulate diverse physiological processes, including specialized metabolism. These low molecular weight compounds are common in Streptomyces species and display species-specific structural differences. Recently, unusual gamma-butyrolactone natural products called salinipostins were isolated from the marine actinomycete genus Salinispora based on their anti-malarial properties. As the salinipostins possess a rare phosphotriester motif of unknown biosynthetic origin, we set out to explore its construction by the widely conserved 9-gene spt operon in Salinispora species. We show through a series of in vivo and in vitro studies that the spt gene cluster dually encodes the saliniphostins and newly identified A-factor-like gamma-butyrolactones (Sal-GBLs). Remarkably, homologous biosynthetic gene clusters are widely distributed amongst many actinomycete genera, including Streptomyces, suggesting the significance of this operon in bacteria.

HIV-1 integrase inhibitors that block HIV-1 replication in infected cells. Planning synthetic derivatives from natural products

2003 ◽  
Vol 75 (2-3) ◽  
pp. 195-206 ◽  
Author(s):  
Roberto Di Santo ◽  
Roberta Costi ◽  
Marino Artico ◽  
E. Tramontano ◽  
P. La Colla ◽  
...  
Keyword(s):  
Natural Products ◽  
Clinical Approach ◽  
Strand Transfer ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Acquired Immunodeficiency ◽  
High Cytotoxicity ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Combination therapy using reverse transcriptase (RT) and protease (PR) inhibitors is currently the best clinical approach in combatting acquired immunodeficiency syndrome (AIDS), caused by infection from the human immunodeficiency virus type 1 (HIV-1). However, the emergence of resistant strains calls urgently for research on inhibitors of further viral targets such as integrase (IN), the enzyme that catalyzes the integration of the proviral DNA into the host chromosomes. Recently, we started studies on new IN inhibitors as analogs of natural products, characterized by one or two 3,4-dihydroxycinnamoyl moieties, which were proven to be IN inhibitors in vitro. Then, we designed and synthesized a number of derivatives sharing 3,4 dihydroxycinnamoyl groups, obtaining potent IN inhibitors active at submicromolar concentrations. Unfortunately, these derivatives lacked antiretroviral activity, probably owing to their high cytotoxicity. So we designed a number of 3,4,5-trihydroxycinnamoyl derivatives as less-cytotoxic IN inhibitors, which were proven to be antiretrovirals in cell-based assays. Finally, we designed and synthesized a number of aryldiketohexenoic acids, strictly related to the aryldiketo acid series recently reported by Merck Company, which were shown to be potent antiretroviral agents endowed with anti-IN activities either in 3' processing or in strand transfer steps.

scholarly journals Cyclic Dipeptides Produced by Marine Sponge-Associated Bacteria as Quorum Sensing Signals

2014 ◽  
Vol 9 (2) ◽  
pp. 1934578X1400900
Author(s):  
Gennaro Roberto Abbamondi ◽  
Salvatore De Rosa ◽  
Carmine Iodice ◽  
Giuseppina Tommonaro
Keyword(s):  
Quorum Sensing ◽  
Quorum Quenching ◽  
Marine Sponges ◽  
Bacterial Strains ◽  
Signal Molecule ◽  
Associated Bacteria ◽  
Cyclic Dipeptides ◽  
Sponge Associated Bacteria ◽  
Dysidea Avara ◽  
Quorum Sensing Signals

Four bacterial strains belonging to the genera Vibrio, Pseudoalteromonas and Photobacterium were isolated from the marine sponges Dysidea avara and Geodia cynodium. A Bacillus strain was isolated from Ircinia variabilis. A screening of molecules involved in quorum sensing (QS) was carried out by TLC-overlay and a new “plate T-streak” test. To analyze quorum quenching (QQ), a plate T-streak was performed with Chromobacterium violaceum. Strains of Vibrio isolated from both marine sponges and a strain of Photobacterium isolated from G. cynodium, activated QS bioreporters. A strain of Pseudoalteromonas isolated from D. avara showed QQ activity. Finally, it is reported that cyclic dipeptides isolated from strains of Vibrio sp. and Bacillus sp. (isolated from D. avara and I. variabilis, respectively) were involved in the QS mechanism. The simultaneous presence of bacteria that showed contrasting responses in bioassays for QS signal molecule synthesis in marine sponges could add an interesting dimension to the signalling interactions which may be happening in sponges.

scholarly journals Potency of sponge-associated bacteria producing bioactive compounds as biological control of vibriosis on shrimp

2017 ◽  
Vol 16 (1) ◽  
pp. 41
Author(s):  
Adityawati Fajar Rini ◽  
Munti Yuhana ◽  
Aris Tri Wahyudi
Keyword(s):  
16S Rrna ◽  
Bioactive Compounds ◽  
Polyketide Synthase ◽  
Sea Water ◽  
White Shrimp ◽  
Pathogenicity Test ◽  
Associated Bacteria ◽  
Sponge Associated Bacteria

<p class="Pa3"><strong>ABSTRACT </strong></p><p> </p><p class="Pa5"><em>Vibrio </em>sp. is a pathogen that causes a decrease in white shrimp production. Sponge-associated bacteria are known as bioactive compounds producer in marine habitat, such as antibacteria, which can be an alternative solution in preventing vibriosis. Thus, this study was aimed to obtain a sponge-associated bacteria biocontroller to inhibit vibriosis <em>in vitro</em>, <em>in vivo </em>and also in 16S-rRNA, Non-ribosomal peptide synthase (NRPS) and polyketide synthase (PKS) genes to demonstrate its ability of synthesizing (bioactive). <em>Aaptos </em>sp. and <em>Hyrtios </em>sp. sponges were collected from Pramuka Island, Jakarta. The isolation using sea water complete (SWC) and zobel marine agar (ZMA) resulted in 174 isolates, and a total of 69 isolates were successfully screened based on their antibacterial compound activity, while a total of 47 isolates were observed to have negative hemolysis (in hemolytic test). The pathogenicity test used twelve selected isolates, that have broad spectrums of antibacteria activity and hemolysis negative, showed that the selected isolates were not pathogenic to post-larva shrimp, indicating that shrimp survival rate (pathogenicity test) did not significantly differ (P&gt;0,05) compared to the negative control. Genetic analysis based on 16S-rRNA revealed three genera groups that belonged to <em>Pseudomonas</em>, <em>Staphylococcus</em>, and <em>Alcaligenes</em>. NRPS and PKS genes detection using PCR engendered four potential bacteria isolates, which have the NRPS gene only, and one isolate having the PKS gene only and one isolate having both NRPS and PKS genes, proving that the bacteria produce bioactive compounds.</p><p> </p><p class="Pa5">Keywords: NRPS, PKS, anti-vibriosis, white shrimp</p><p> </p><p> </p><p class="Pa3"><strong>ABSTRAK </strong></p><p> </p><p class="Pa5"><em>Vibrio </em>sp. merupakan salah satu bakteri patogen yang menyebabkan penurunan produksi udang. Bakteri yang berasosiasi dengan spons diketahui merupakan produsen senyawa bioaktif perairan salah satunya sebagai antibakteri. Hal ini dapat menjadi alternatif solusi dalam penanggulangan vibriosis. Penelitian ini bertujuan untuk memperoleh isolat bakteri asosiasi spons yang mempunyai kemampuan dalam menghambat vibriosis secara <em>in vitro</em>, <em>in vivo </em>dan mendeteksi gen 16S-rRNA, nonribosomal peptide synthase (NRPS) serta polyketide synthase (PKS) untuk memastikan kemampuan mensintesis senyawa bioaktif. Spons <em>Aaptos </em>sp. dan <em>Hyrtios </em>sp. berhasil dikoleksi dari perairan Pulau Pramuka, Kep. Seribu Jakarta. Isolasi bakteri dengan menggunakan media sea water complete (SWC) dan zobel marine agar (ZMA) diperoleh 174 isolat. Sebanyak 69 isolat terdeteksi memiliki aktivitas antibakteri. Uji hemolisis menunjukkan 47 isolat adalah hemolisis negatif. Uji patogenisitas menggunakan 12 isolat terpilih yang memiliki spektrum luas dan hemolisis negatif. Hasil uji patogenisitas tehadap 12 isolat menunjukkan bahwa semua isolat tidak bersifat patogen terhadap pascalarva udang vaname. Hal ini dibuktikan dengan sintasan pascalarva udang vaname yang tidak berbeda nyata (P&gt;0,05) dengan kontrol negatif. Hasil uji tantang terhadap <em>Vibrio harveyi </em>diketahui sintasan pascalarva udang vaname (70±5,0–90±0,0%) memiliki perbedaan yang signifikan jika dibandingkan dengan kontrol positif (38,3±2,9%). Berdasarkan analisis sekuen gen 16S-rRNA, menunjukkan bahwa isolat-isolat tersebut memiliki kemiripan dengan genus <em>Pseudomonas</em>, <em>Staphylococcus </em>dan <em>Alcaligenes</em>. Deteksi gen NRPS dan PKS menggunakan PCR diperoleh empat isolat bakteri memiliki hanya gen NRPS, satu isolat memiliki hanya gen PKS, dan satu isolat memiliki kedua gen NRPS-PKS. Hal ini membuktikan bahwa keenam isolat memiliki potensi sebagai penghasil senyawa bioaktif.</p><p> </p><p>Kata kunci: NRPS, PKS, antivibriosis, udang vaname</p>

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