Monitoring bacterial diversity of the marine sponge Ircinia strobilina upon transfer into aquaculture

Marine sponges in the genus Ircinia are known to be good sources of secondary metabolites with biological activities. A major obstacle in the development of sponge-derived metabolites is the difficulty in ensuring an economic, sustainable supply of the metabolites. A promising strategy is the ex situ culture of sponges in closed or semiclosed aquaculture systems. In this study, the marine sponge Ircinia strobilina (order Dictyoceratida: family Irciniidae) was collected from the wild and maintained for a year in a recirculating aquaculture system. Microbiological and molecular community analyses were performed on freshly collected sponges and sponges maintained in aquaculture for 3 months and 9 months. Chemical analyses were performed on wild collected sponges and individuals maintained in aquaculture for 3 months and 1 year. Denaturing gradient gel electrophoresis was used to assess the complexity of and to monitor changes in the microbial communities associated with I. strobilina. Culture-based and molecular techniques showed an increase in the Bacteroidetes and Alpha- and Gammaproteobacteria components of the bacterial community in aquaculture. Populations affiliated with Beta- and Deltaproteobacteria, Clostridia, and Planctomycetes emerged in sponges maintained in aquaculture. The diversity of bacterial communities increased upon transfer into aquaculture.     

Marine natural product peptides with therapeutic potential: Chemistry,biosynthesis, and pharmacology

The oceans are a uniquely rich source of bioactive metabolites, of which sponges have been shown to be among the most prolific producers of diverse bioactive secondary metabolites with valuable therapeutic potential. Much attention has been focused on marine bioactive peptides due to their novel chemistry and diverse biological properties. As summarized in this review, marine peptides are known to exhibit various biological activities such as antiviral, anti-proliferative, antioxidant, anti-coagulant, anti-hypertensive, anti-cancer, antidiabetic, antiobesity, and calcium-binding activities. This review focuses on the chemistry and biology of peptides isolated from sponges, bacteria, cyanobacteria, fungi, ascidians, and other marine sources. The role of marine invertebrate microbiomes in natural products biosynthesis is discussed in this review along with the biosynthesis of modified peptides from different marine sources. The status of peptides in various phases of clinical trials is presented, as well as the development of modified peptides including optimization of PK and bioavailability.     

海洋动物来源微生物的共培养研究进展

近年来,由于一些新疾病的发生和细菌耐药性的出现,微生物来源次级代谢产物的筛选重复率越来越高,微生物一些代谢基因在现有实验室条件下无法表达,所以需要发现新的微生物资源,同时找到激活微生物代谢产物基因的方法。海洋动物体内蕴含着大量的共附生微生物资源,可以产生很多具有生物活性的化合物,是潜在的药用资源。本文综述了近年来海洋动物(海鞘、海绵、珊瑚和海葵等)来源的微生物进行共培养的研究策略,包括共培养菌株的选择、共培养条件、群体感应和信号分子对共培养菌株的影响,以及不同种类微生物间的共培养实例。共培养与单培养相比,增加了次级代谢产物的种类,提高了次级代谢产物的生物活性或产量。共培养的研究有助于发现新的海洋动物来源微生物的活性天然产物,为海洋药物的开发提供新思路。     

海洋曲霉属真菌抗菌活性物质的研究进展

海洋微生物由于其独特的生存环境造就了许多结构新颖、具有特殊生物活性的代谢产物。随着科学技术的发展,科学界掀起了对海洋微生物代谢物的研究浪潮。近年来的研究表明,海洋曲霉属真菌及其次级代谢产物具有抗肿瘤、抗菌、抗病毒等生物活性。通过查阅文献与资料,对近年来海洋曲霉属真菌及其次级代谢产物的化学结构及生物活性研究与开发的进展进行综述总结,以期有助于后续研究及应用。     

Anti-protease and Immunomodulatory Activities of Bacteria Associated with Caribbean Sponges

Marine sponges and their associated bacteria have been proven to be a rich source of novel secondary metabolites with therapeutic usefulness in cancer, infection, and autoimmunity. In this study, 79 strains belonging to 20 genera of the order Actinomycetales and seven strains belonging to two genera of the order Sphingomonadales were cultivated from 18 different Caribbean sponges and identified by 16S rRNA gene sequencing. Seven of these strains are likely to represent novel species. Crude extracts from selected strains were found to exhibit protease inhibition against cathepsins B and L, rhodesain, and falcipain-2 as well as immunomodulatory activities such as induction of cytokine release by human peripheral blood mononuclear cells. These results highlight the significance of marine sponge-associated bacteria to produce bioactive secondary metabolites with therapeutic potential in the treatment of infectious diseases and disorders of the immune system.     

Some results and prospects of studies in the area of marine biochemistry and biotechnology]

Recent studies on bioactive metabolites from marine macro- and microorganisms are reviewed with 83 refs. Structures of new sulphated and glycosylated secondary metabolites, which have been reported to have antifungal, immunomodulatory, and cytotoxic properties, are given. Some peculiarities of biosynthesis of natural compounds in marine organisms are revealed. It was shown that some natural products, isolated earlier from sponges, are produced by microbial symbionts. Different physiological activities associated with 8000 marine microbial (mainly symbiotic) strains are discussed as well as some prospects of marine biochemistry and biotechnology development.     

Discovery of novel metabolites from marine actinomycetes

Recent findings from culture-dependent and culture-independent methods have demonstrated that indigenous marine actinomycetes exist in the oceans and are widely distributed in different marine ecosystems. There is tremendous diversity and novelty among the marine actinomycetes present in marine environments. Progress has been made to isolate novel actinomycetes from samples collected at different marine environments and habitats. These marine actinomycetes produce different types of new secondary metabolites. Many of these metabolites possess biological activities and have the potential to be developed as therapeutic agents. Marine actinomycetes are a prolific but underexploited source for the discovery of novel secondary metabolites.     

Inhibitors of Protein Tyrosine Phosphatase 1B from Marine Natural Products

The ocean is a capacious area with the most abundant biological resources on the earth. The particularity of the marine ecological environment (high pressure, high salt, and hypoxia) makes the marine species survival competition fiercely, forcing many marine organisms in the process of life to produce a great deal of secondary metabolites with special structures and biological activities. In this article, 118 natural products which were isolated from four kinds of marine organisms, sponges, algae, soft corals and fungus, showing PTP1B inhibitory activity were summarized from 2010 to 2016, which may become the leading compounds towards treating Diabetes mellitus (DM). What's more, we briefly summarized the structure–activity relationship of PTP1B inhibitors.     

The five bromotryptophans

Summary. The five regioisomeric bromotryptophans (BrTrps) play an important role in the life of sponges and lower marine invertebrates. These bromo-amino acids, which are formed by post-translational modifications, are not found in nature in their free state, but rather are involved in more complex structures. Any of the BrTrps can be part of a peptide, a cyclic peptide, an indole alkaloid, an ergot alkaloid, a macrocycle and others. The present review covers the synthesis, physical and spectroscopic properties of the five BrTrps. It also describes the many exiting pharmacological and biological activities played by the BrTrps and by various secondary metabolites containing brominated tryptophan moieties. Of special interest are cyclic peptides containing the 2-BrTrp unit, which were isolated from marine sponges e.g. konbamide, orbiculamide A, the various keramamides, jaspamide eusynstyelamide and more. Important families of non-cyclic peptides containing the 6-BrTrp, include the styelins, the conotoxins, the cathelicidins and several constrained macrocyclic peptides. Many marine secondary BrTrp-containing, non-peptidic metabolites also display a remarkable spectrum of bioactivities, which can be harnessed for therapeutic and other purposes. Examples are: barettin, bromotryptanthrin, tetraacetyl clionamide, cyclocinamide A, clavicipitic acid, various brominated β-carbolines. In this review we have presented the various synthetic routes leading to the preparation of the five BrTrps and many of its derivatives. Also, we have introduced the reader to many synthetic routes leading to BrTrp-containing non-peptidic natural products. Although the functional role of the various compounds in the human body is only poorly understood, its effects were extensively studied. Almost all of these compounds exhibit important therapeutic properties e.g. antifungal, antimicrobial, antihelmintic, insecticidal ichthyotoxic and anticancer activity. In the present review attempts have been made to provide synopsis, synthesis and symbiosis of chemical and biological actions, which may provide future guidance and facilitate further research in this area.     

Secondary Metabolites as Mediators of Trophic Interactions Among Antarctic Marine Organisms

Secondary metabolites are widespread among lower phyla and understandingtheir functional role(s) in the producing organism has beenunder study in recent decades. Considerable progress has beenmade in understanding chemical ecological interactions amongterrestrial organisms, and similar research in the marine realmhas been initiated in recent years. Polar regions are more difficultto access and thus progress has been slower. Nevertheless, theextreme and often unique marine environments surrounding Antarcticaas well as the many unusual trophic interactions in antarcticmarine communities might well be expected to select for novelsecondary metabolites and/or novel functional roles for secondarymetabolites. Indeed, recent studies have documented novel, chemically-mediatedinteractions between molluscs and amphipods, between algae,urchins and anemones, and between sponges and their predators.The Porifera are the dominant phylum on the McMurdo Sound benthos,and representatives of this phylum have been shown to elaboratesea star feeding deterrents, inhibitors of fouling or infectiousorganisms, and metabolites which mediate predation via moltinhibition. As a result of studies on Antarctic sponges, newinsights into functional roles of pigments and the ability ofsponges to sequester metabolites have been gained, and a newmechanism of chemical defense has been described. Herein wedescribe recent results of our studies of trophic interactionsbetween sponges and their predators that are mediated by specificsponge secondary metabolites. Moreover, we highlight unusualchemically-mediated interactions in antarctic marine invertebratesother than sponges.     

专性海洋放线菌盐孢菌的研究进展

盐孢菌属(Salinispora)作为首个被报道的专性海洋放线菌,主要分布于热带和亚热带海洋沉积环境中,在海绵、海鞘中也有发现。与其他大多数放线菌一样,盐孢菌属的菌株可以产生大量具有抗细菌、抗病毒、抗肿瘤细胞活性、结构新颖的次级代谢产物且表现出物种特异性。全基因组序列分析显示,盐孢菌属菌株基因组中超过10%的基因序列与次级代谢产物合成相关,但绝大多数生物合成基因簇编码的产物未被发现,表明盐孢菌属还存在巨大的生物合成潜能,有待深入发掘。目前新的培养方法、测序技术及生物信息学、基因组发掘技术、合成生物学技术的发展对提升盐孢菌属菌株新型药物的生产潜力发挥重要作用。本文对盐孢菌属的物种多样性、系统分类与化合物发现等方面的研究进行了系统综述。     

Pharmaceutically active secondary metabolites of marine actinobacteria

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future.     

Marine Sponges as Pharmacy

Marine sponges have been considered as a gold mine during the past 50 years, with respect to the diversity of their secondary metabolites. The biological effects of new metabolites from sponges have been reported in hundreds of scientific papers, and they are reviewed here. Sponges have the potential to provide future drugs against important diseases, such as cancer, a range of viral diseases, malaria, and inflammations. Although the molecular mode of action of most metabolites is still unclear, for a substantial number of compounds the mechanisms by which they interfere with the pathogenesis of a wide range of diseases have been reported. This knowledge is one of the key factors necessary to transform bioactive compounds into medicines. Sponges produce a plethora of chemical compounds with widely varying carbon skeletons, which have been found to interfere with pathogenesis at many different points. The fact that a particular disease can be fought at different points increases the chance of developing selective drugs for specific targets.     

Drugs from the seas - current status and microbiological implications

The oceans are the source of a large group of structurally unique natural products that are mainly accumulated in invertebrates such as sponges, tunicates, bryozoans, and molluscs. Several of these compounds (especially the tunicate metabolite ET-743) show pronounced pharmacological activities and are interesting candidates for new drugs primarily in the area of cancer treatment. Other compounds are currently being developed as an analgesic (ziconotide from the mollusc Conus magus) or to treat inflammation. Numerous natural products from marine invertebrates show striking structural similarities to known metabolites of microbial origin, suggesting that microorganisms (bacteria, microalgae) are at least involved in their biosynthesis or are in fact the true sources of these respective metabolites. This assumption is corroborated by several studies on natural products from sponges that proved these compounds to be localized in symbiotic bacteria or cyanobacteria. Recently, molecular methods have successfully been applied to study the microbial diversity in marine sponges and to gain evidence for an involvement of bacteria in the biosynthesis of the bryostatins in the bryozoan Bugula neritina.     

Convergent Antifouling Activities of Structurally Distinct Bioactive Compounds Synthesized Within Two Sympatric Haliclona Demosponges

A wide range of sessile and sedentary marine invertebrates synthesize secondary metabolites that have potential as industrial antifoulants. These antifoulants tend to differ in structure, even between closely related species. Here, we determine if structurally divergent secondary metabolites produced within two sympatric haliclonid demosponges have similar effects on the larvae of a wide range of benthic competitors and potential fouling metazoans (ascidians, molluscs, bryozoans, polychaetes, and sponges). The sponges Haliclona sp. 628 and sp. 1031 synthesize the tetracyclic alkaloid, haliclonacyclamine A (HA), and the long chain alkyl amino alcohol, halaminol A (LA), respectively. Despite structural differences, HA and LA have identical effects on phylogenetically disparate ascidian larvae, inducing rapid larval settlement but preventing subsequent metamorphosis at precisely the same stage. HA and LA also have similar effects on sponge, polychaete, gastropod and bryozoan larvae, inhibiting both settlement and metamorphosis. Despite having identical roles in preventing fouling and colonisation, HA and LA differentially affect the physiology of cultured HeLa human cells, indicating they have different molecular targets. From these data, we infer that the secondary metabolites within marine sponges may emerge by varying evolutionary and biosynthetic trajectories that converge on specific ecological roles.     

Principles of Biofouling Protection in Marine Sponges: A Model for the Design of Novel Biomimetic and Bio-inspired Coatings in the Marine Environment?

The process of biofouling of marine structures and substrates, such as platforms or ship hulls, proceeds in multiple steps. Soon after the formation of an initial conditioning film, formed via the adsorption of organic particles to natural or man-made substrates, a population of different bacterial taxa associates under the formation of a biofilm. These microorganisms communicate through a complex quorum sensing network. Macro-foulers, e.g., barnacles, then settle and form a fouling layer on the marine surfaces, a process that globally has severe impacts both on the economy and on the environment. Since the ban of tributyltin, an efficient replacement of this antifouling compound by next-generation antifouling coatings that are environmentally more acceptable and also showing longer half-lives has not yet been developed. The sponges, as sessile filter-feeder animals, have evolved antifouling strategies to protect themselves against micro- and subsequent macro-biofouling processes. Experimental data are summarized and suggest that coating of the sponge surface with bio-silica contributes to the inhibition of the formation of a conditioning film. A direct adsorption of the surfaces by microorganisms can be impaired through poisoning the organisms with direct-acting secondary metabolites or toxic peptides. In addition, first, compounds from sponges have been identified that interfere with the anti-quorum sensing network. Sponge secondary metabolites acting selectively on diatom colonization have not yet been identified. Finally, it is outlined that direct-acting secondary metabolites inhibiting the growth of macro-fouling animals and those that poison the multidrug resistance pump are available. It is concluded that rational screening programs for inhibitors of the complex and dynamic problem of biofilm production, based on multidisciplinary studies and using sponges as a model, are required in the future.     

Marine actinomycetes as an emerging resource for the drug development pipelines

Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinomycetes from terrestrial sources have been studied and screened since the 1950s, yielding many important anti-infective and anti-cancer drugs. However, frequent re-discovery of the same compounds in terrestrial actinomycetes have made them less attractive for screening programs in the recent years. At the same time, actinomycetes isolated from the marine environment currently receive considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. This review highlights achievements and challenges in the isolation of marine actinomycetes, some examples of bioactive metabolites identified by conventional screening, and presents new developments in the field of genome mining and heterologous expression of biosynthetic gene clusters leading to the discovery of novel compounds.     

Methods for isolation, purification and structural elucidation of bioactive secondary metabolites from marine invertebrates

In the past few decades, marine natural products bioprospecting has yielded a considerable number of drug candidates. Two marine natural products have recently been admitted as new drugs: Prialt (also known as ziconotide) as a potent analgesic for severe chronic pain and Yondelis (known also as trabectedin or E-743) as antitumor agent for the treatment of advanced soft tissue sarcoma. In this protocol, methods for bioactivity-guided isolation, purification and identification of secondary metabolites from marine invertebrates such as sponges, tunicates, soft corals and crinoids are discussed. To achieve this goal, solvent extraction of usually freeze-dried sample of marine organisms is performed. Next, the extract obtained is fractionated by liquid-liquid partitioning followed by various chromatographic separation techniques including thin layer chromatography, vacuum liquid chromatography, column chromatography (CC) and preparative high-performance reversed-phase liquid chromatography. Isolation of bioactive secondary metabolites is usually monitored by bioactivity assays, e.g., antioxidant (2,2-diphenyl-1-picryl hydrazyl) and cytotoxicity (microculture tetrazolium) activities that ultimately yield the active principles. Special care should be taken when performing isolation procedures adapted to the physical and chemical characteristics of the compounds isolated, particularly their lipo- or hydrophilic characters. Examples of isolation of compounds of different polarities from extracts of various marine invertebrates will be presented in this protocol. Structure elucidation is achieved using recent spectroscopic techniques, especially 2D NMR and mass spectrometry analysis.     

Biomedicinals from the phytosymbionts of marine invertebrates: a molecular approach

Marine invertebrate animals such as sponges, gorgonians, tunicates and bryozoans are sources of biomedicinally relevant natural products, a small but growing number of which are advancing through clinical trials. Most metazoan and anthozoan species harbour commensal microorganisms that include prokaryotic bacteria, cyanobacteria (blue-green algae), eukaryotic microalgae, and fungi within host tissues where they reside as extra- and intra-cellular symbionts. In some sponges these associated microbes may constitute as much as 40% of the holobiont volume. There is now abundant evidence to suggest that a significant portion of the bioactive metabolites thought originally to be products of the source animal are often synthesized by their symbiotic microbiota. Several anti-cancer metabolites from marine sponges that have progressed to pre-clinical or clinical-trial phases, such as discodermolide, halichondrin B and bryostatin 1, are thought to be products derived from their microbiotic consortia. Freshwater and marine cyanobacteria are well recognised for producing numerous and structurally diverse bioactive and cytotoxic secondary metabolites suited to drug discovery. Sea sponges often contain dominant taxa-specific populations of cyanobacteria, and it is these phytosymbionts (= photosymbionts) that are considered to be the true biogenic source of a number of pharmacologically active polyketides and nonribosomally synthesized peptides produced within the sponge. Accordingly, new collections can be pre-screened in the field for the presence of phytobionts and, together with metagenomic screening using degenerate PCR primers to identify key polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes, afford a biodiscovery rationale based on the therapeutic prospects of phytochemical selection. Additionally, new cloning and biosynthetic expression strategies may provide a sustainable method for the supply of new pharmaceuticals derived from the uncultured phytosymbionts of marine organisms.     

Major bioactive metabolites from marine fungi: A Review

Biologists and chemists of the world have been attracted towards marine natural products for the last five decades. Approximately 16,000 marine natural products have been isolated from marine organisms which have been reported in approximately 6,800 publications, proving marine microorganisms to be a invaluable source for the production of novel antibiotic, anti tumor, and anti inflammatory agents. The marine fungi particularly those associated with marine alga, sponge, invertebrates, and sediments appear to be a rich source for secondary metabolites, possessing Antibiotic, antiviral, antifungal and antiyeast activities. Besides, a few growth stimulant properties which may be useful in studies on wound healing, carcinogenic properties, and in the study of cancers are reported. Recent investigations on marine filamentous fungi looking for biologically active secondary metabolites indicate the tremendous potential of them as a source of new medicines. The present study reviews about some important bioactive metabolites reported from marine fungal strains which are anti bacterial, anti tumour and anti inflammatory in action. It highlights the chemistry and biological activity of the major bioactive alkaloids, polyketides, terpenoids, isoprenoid and non-isoprenoid compounds, quinones, isolated from marine fungi.